Stathmin-2 (SCG10)

Stathmin-2 (SCG10)

title: Stathmin-2 (SCG10)
description: Page for Stathmin-2 (SCG10)
published: true
tags: kind:protein, section:proteins, state:published
editor: markdown
pageId: 1517
dateCreated: "2026-02-27T23:26:51.397Z"
dateUpdated: "2026-03-22T17:25:31.891Z"
refs:
klim2019:
authors: Klim JR, Williams LA, Limone F, et al.
title: (2019). ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair. Nature Neuroscience, 22(2):167-179. DOI
year: 2019
doi: 10.1038/s41593-018-0300-4
melamed2019:
authors: Melamed Z, et al.
title: (2019). Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration. Nature Neuroscience, 22(2):180-190. DOI
year: 2019
doi: 10.1038/s41593-018-0293-z
baughn2023:
authors: Baughn MW, et al.
title: (2023). Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science, 379(6637):1140-1149. DOI
year: 2023
doi: 10.1126/science.abq5622
guerra2023:
authors: Guerra San Juan I, et al.
title: ''(2023). SCG10 is required for peripheral axon maintenance and regeneration in mice. J Cell Biol, 222(7):e202206030. PMID:37283026''
year: 2023
pmid: '37283026'
bhola2025:
authors: Bhola T, et al.
title: (2025). Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin. PNAS, 122(21).

...

Stathmin-2 (SCG10)

title: Stathmin-2 (SCG10)
description: Page for Stathmin-2 (SCG10)
published: true
tags: kind:protein, section:proteins, state:published
editor: markdown
pageId: 1517
dateCreated: "2026-02-27T23:26:51.397Z"
dateUpdated: "2026-03-22T17:25:31.891Z"
refs:
klim2019:
authors: Klim JR, Williams LA, Limone F, et al.
title: (2019). ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair. Nature Neuroscience, 22(2):167-179. DOI
year: 2019
doi: 10.1038/s41593-018-0300-4
melamed2019:
authors: Melamed Z, et al.
title: (2019). Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration. Nature Neuroscience, 22(2):180-190. DOI
year: 2019
doi: 10.1038/s41593-018-0293-z
baughn2023:
authors: Baughn MW, et al.
title: (2023). Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science, 379(6637):1140-1149. DOI
year: 2023
doi: 10.1126/science.abq5622
guerra2023:
authors: Guerra San Juan I, et al.
title: ''(2023). SCG10 is required for peripheral axon maintenance and regeneration in mice. J Cell Biol, 222(7):e202206030. PMID:37283026''
year: 2023
pmid: '37283026'
bhola2025:
authors: Bhola T, et al.
title: (2025). Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin. PNAS, 122(21). PMID:40392845
year: 2025
pmid: '40392845'
agra2024:
authors: Agra Almeida Quadros AR, et al.
title: (2024). Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer's Disease. Acta Neuropathologica, 147:9. DOI
year: 2024
doi: 10.1007/s00401-023-02655-0
krus2022:
authors: Krus KL, et al.
title: ''(2022). Stathmin-2: adding another piece to the puzzle of TDP-43 proteinopathies. JCI, 132(7):e142854. DOI''
year: 2022
doi: 10.1172/JCI142854
beri2024:
authors: Beri S, et al.
title: (2024). Targeting STMN2 for neuroprotection in Spinal Muscular Atrophy. Cell Mol Life Sci, 81:487. DOI
year: 2024
doi: 10.1007/s00018-024-05550-3
quralis2026:
title: QurAlis Corporation. (2026). QurAlis demonstrates effects on disease progression and target engagement in ANQUR clinical trial of QRL-201. Press release
year: 2026
url: https://www.biospace.com/press-releases/quralis-demonstrates-effects-on-disease-progression-and-target-engagement-in-anqur-clinical-trial-of-qrl-201-a-first-in-class-precision-medicine-in-development-for-sporadic-als
brown2022:
authors: Brown AL, et al.
title: (2022). TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A. Nature, 603(7899):131-137. DOI
year: 2022
doi: 10.1038/s41586-022-04436-3
ma2022:
authors: Ma XR, et al.
title: (2022). TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A. Nature, 603(7899):124-130. DOI
year: 2022
doi: 10.1038/s41586-022-04424-7
seddighi2024:
authors: Seddighi S, et al.
title: (2024). Loss of TDP-43 induces synaptic dysfunction that is rescued by UNC13A splice-switching ASOs. J Clin Invest, 134(13):e177567. DOI
year: 2024
doi: 10.1172/JCI177567
humphrey2025:
authors: Humphrey J, et al.
title: (2025). Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathies. bioRxiv. DOI
year: 2025
doi: 10.1101/2025.12.01.691001
allen:
authors: '-'
title: Allen Brain Atlas
url: https://brain-map.org
allena:
authors: '-'
title: 'Allen Human Brain Atlas: Stathmin-2 search'
url: https://human.brain-map.org/microarray/search/show?search_term=Stathmin-2
allenb:
authors: '-'
title: 'Allen Mouse Brain Atlas: Stathmin-2 search'
url: https://mouse.brain-map.org/search/index.html?query=Stathmin-2
allenc:
authors: '-'
title: Allen Cell Type Atlas
url: https://portal.brain-map.org/atlases-and-data/rnaseq
brainspan:
authors: '-'
title: BrainSpan Developmental Transcriptome
url: https://www.brainspan.org
stmn:
title: '- stmn2 — Gene encoding stathmin-2'
tdp:
title: '- tdp-43 — Key regulator of STMN2 splicing'
tardbp:
title: '- tardbp — Gene encoding TDP-43'
unca:
title: '- unc13a — Other major TDP-43 cryptic splicing target'
tdpproteinopathy:
title: '- tdp-43-proteinopathy — Mechanism of TDP-43 pathology'
als:
title: '- als — Disease where stathmin-2 loss is pathogenic'
ftd:
title: '- ftd — FTLD-TDP involves STMN2 cryptic splicing'
motorneurons:
title: '- motor-neurons — Primary cell type expressing stathmin-2'
nflprotein:
title: '- nfl-protein — Complementary neurodegeneration biomarker## See Also'
proteins:
title: ''- Proteins Index''
alzheimers:
title: '- alzheimers'
parkinsons:
title: '- parkinsons'
neuroinflammation:
title: '- neuroinflammation'
uniprot:
authors: '-'
title: 'UniProt: Q93045'
url: https://www.uniprot.org/uniprot/Q93045
genecards:
authors: '-'
title: 'GeneCards: STMN2'
url: https://www.genecards.org/cgi-bin/carddisp.pl?gene=STMN2
clinicaltrialsgov:
authors: '-'
title: 'ClinicalTrials.gov: QRL-201'
url: https://clinicaltrials.gov/search?term=QRL-201
alzforum:
authors: '-'
title: 'ALZFORUM: QRL-201'
url: https://www.alzforum.org/therapeutics/qrl-201

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Stathmin-2 (SCG10)</th>
</tr>
<tr> [@bhola2025]
<td class="label">Protein Name</td> [@agra2024]
<td><strong>Stathmin-2</strong></td> [@krus2022]
</tr> [@beri2024]
<tr> [@quralis2026]
<td class="label">Gene</td> [@brown2022]
<td>[STMN2](/entities/stmn2)</td> [@ma2022]
</tr> [@seddighi2024]
<tr> [@humphrey2025]
<td class="label">UniProt</td> [@allen]
<td><a href="https://www.uniprot.org/uniprot/Q93045" target="_blank">Q93045</a></td> [@allena]
</tr> [@allenb]
<tr> [@allenc]
<td class="label">PDB Structures</td> [@brainspan]
<td>No full-length structure available; stathmin-like domain modeled</td> [@stmn]
</tr> [@tdp]
<tr> [@tardbp]
<td class="label">Molecular Weight</td> [@unca]
<td>~20.8 kDa (179 amino acids)</td> [@tdpproteinopathy]
</tr> [@als]
<tr> [@ftd]
<td class="label">Localization</td> [@motorneurons]
<td>Growth cones, axonal vesicles, Golgi membranes</td> [@nflprotein]
</tr> [@proteins]
<tr> [@alzheimers]
<td class="label">Protein Family</td> [@parkinsons]
<td>Stathmin family (STMN1-4)</td> [@neuroinflammation]
</tr> [@uniprot]
</table> [@genecards]

Stathmin-2 (SCG10)

Introduction

Stathmin 2 (Scg10) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes. [@clinicaltrialsgov]

Overview

Stathmin-2 (also known as SCG10, Superior Cervical Ganglion 10) is a neuron-enriched phosphoprotein of the stathmin family that plays a critical role in axonal growth, maintenance, and regeneration. Encoded by the [stmn2](/proteins/stmn2-protein) gene on chromosome 8q21.13, stathmin-2 is one of the most abundantly expressed proteins in [motor-neurons](/cell-types/motor-neurons) and is essential for axonal repair after injury ([Klim et al., 2019](https://pubmed.ncbi.nlm.nih.gov/30643292/)). Stathmin-2 has become the focus of intense therapeutic development following the discovery that its loss — through cryptic splicing of STMN2 mRNA upon [tdp-43](/proteins/tdp-43) nuclear depletion — is a major pathogenic mechanism in [als](/diseases/als), [ftd](/diseases/ftd), and other [TDP-43](/mechanisms/tdp-43-proteinopathy) proteinopathies. The first-in-class therapeutic QRL-201 (Quralis), an antisense oligonucleotide designed to restore stathmin-2 expression, entered clinical trials in 2023 and has shown early signals of disease modification in ALS patients. [@alzforum]

Structure

Domain Architecture

Stathmin-2 is a 179-amino-acid protein (~20.8 kDa) with three functional domains:

• N-terminal membrane-targeting domain (residues 1-40): contains a palmitoylation site that anchors stathmin-2 to vesicular membranes, particularly in growth cones. This domain distinguishes stathmin-2 from cytoplasmic stathmin (STMN1) and is critical for its subcellular targeting to axonal growth cones and Golgi membranes.
• Regulatory region (residues 40-80): contains phosphorylation sites (Ser62, Ser73) that regulate protein stability and microtubule interactions. Phosphorylation by kinases including [cdk5](/proteins/cdk5) and JNK modulates stathmin-2 activity.
• Stathmin-like domain (SLD) (residues 80-179): shares ~50% homology with the core domain of stathmin (STMN1). Contains a coiled-coil region that can sequester alpha/beta-tubulin heterodimers and promote microtubule catastrophe.

Post-Translational Modifications

Stathmin-2 undergoes several functionally important modifications:

• Palmitoylation: at Cys22, essential for membrane association and growth cone targeting
• Phosphorylation: at Ser62 and Ser73, regulating tubulin binding capacity and protein turnover
• Ubiquitination: targets stathmin-2 for proteasomal degradation, modulating protein levels

Normal Function

Microtubule Dynamics

As a stathmin family member, stathmin-2 can regulate microtubule dynamics by sequestering free tubulin dimers and promoting microtubule depolymerization. However, unlike stathmin (STMN1), stathmin-2 is membrane-associated and concentrated in specific subcellular compartments (growth cones, vesicles) rather than distributed throughout the cytoplasm. This localized regulation of microtubule dynamics is important for growth cone steering and axonal branching.

Axonal Growth and Regeneration

Stathmin-2 is essential for motor axon regeneration after injury. Following peripheral nerve damage, stathmin-2 expression is rapidly upregulated in injured motor [neurons](/entities/neurons), and the protein is transported to regenerating growth cones. Mice lacking stathmin-2 show impaired motor axon regeneration, delayed functional recovery, and defective reinnervation of neuromuscular junctions ([Guerra San Juan et al., 2023](https://pubmed.ncbi.nlm.nih.gov/37283026/)).

Importantly, stathmin-2's role in promoting axon regeneration appears to be independent of its tubulin-binding capacity, suggesting it acts through alternative mechanisms — possibly involving membrane trafficking, signaling at the growth cone, or interactions with other cytoskeletal regulators ([Bhola et al., 2025](https://pubmed.ncbi.nlm.nih.gov/40392845/)).

Neuronal Development

During embryonic development, stathmin-2 is highly expressed in the developing nervous system, where it contributes to axon outgrowth and pathfinding. It is one of the earliest markers of neuronal differentiation and is expressed before neurite extension begins. Expression persists throughout adult life in mature [neurons](/entities/neurons), where stathmin-2 is concentrated in axonal terminals and growth cone-like structures, maintaining ongoing capacity for synaptic remodeling and injury response.

Role in Disease

TDP-43 Proteinopathies — The Cryptic Splicing Mechanism

The central pathogenic mechanism linking stathmin-2 to neurodegeneration involves [tdp-43](/proteins/tdp-43) (encoded by [TARDBP). Under normal conditions, [tdp-43](/proteins/tdp-43) binds to a GU-rich sequence in intron 1 of [stmn2](/proteins/stmn2-protein) pre-mRNA, blocking a cryptic splice-polyadenylation site. When [tdp-43](/proteins/tdp-43) is depleted from the nucleus — as occurs in >97% of [als](/diseases/als) cases and ~45% of [ftd](/diseases/ftd) cases — this cryptic site is activated, producing a truncated mRNA that encodes only 17 amino acids instead of the full 179-amino-acid stathmin-2 protein ([Baughn et al., 2023](https://pubmed.ncbi.nlm.nih.gov/36927019/)).

The resulting near-complete loss of functional stathmin-2 in affected [neurons](/entities/neurons) ablates their capacity for axonal maintenance and regeneration, contributing to progressive neurodegeneration. STMN2 is the most affected RNA target of [tdp-43](/proteins/tdp-43) loss-of-function, and processing of STMN2 pre-mRNA is more sensitive to [tdp-43](/proteins/tdp-43) depletion than [unc13a](/proteins/unc13a), the other major cryptic splicing target, making stathmin-2 restoration a prime therapeutic strategy ([Krus et al., 2022](https://doi.org/10.1172/JCI142854)).

Relationship with UNC13A Cryptic Splicing

[unc13a](/proteins/unc13a) is the second major TDP-43 cryptic splicing target. While STMN2 cryptic exon inclusion affects axonal maintenance, UNC13A cryptic splicing disrupts synaptic vesicle release at the presynaptic terminal. Both STMN2 and UNC13A cryptic exon transcripts are detected in post-mortem tissue from patients with TDP-43 pathology, and their co-occurrence is a hallmark of TDP-43-associated neurodegeneration ([Agra Almeida Quadros et al., 2024](https://pubmed.ncbi.nlm.nih.gov/38175301/)). Loss of TDP-43 induces synaptic dysfunction that can be rescued by UNC13A splice-switching ASOs, complementing the axonal rescue afforded by STMN2 restoration, suggesting that dual targeting of both cryptic exons may be necessary for optimal therapeutic efficacy.

ALS and FTD

In [als](/diseases/als), stathmin-2 protein is dramatically reduced in spinal cord motor [neurons](/entities/neurons) with TDP-43 pathology. The truncated stathmin-2 peptide (first 16 amino acids + 1 cryptic residue) can serve as a neuropathological marker of TDP-43 dysfunction, and truncated STMN2 mRNA has been detected in CSF, positioning it as a potential fluid biomarker for TDP-43 Proteinopathy status ([Melamed et al., 2019](https://doi.org/10.1038/s41593-018-0293-z)). In [ftd](/diseases/ftd) with TDP-43 pathology (FTLD-TDP), stathmin-2 loss occurs in affected frontal and temporal [cortex](/brain-regions/cortex) regions. The degree of STMN2 cryptic exon inclusion correlates with the severity of TDP-43 pathology and clinical disease burden.

Alzheimer's Disease

Cryptic splicing of STMN2 has been detected in [alzheimers](/diseases/alzheimers-disease) patients with TDP-43 co-pathology (~30-50% of AD cases), correlating with TDP-43 pathology burden but not with [Amyloid-Beta](/proteins/amyloid-beta) or [tau](/proteins/tau)[/proteins/[tau-protein](/proteins/tau) deposits ([Agra Almeida Quadros et al., 2024](https://pubmed.ncbi.nlm.nih.gov/38175301/)). This finding suggests that STMN2 cryptic splicing may contribute to the motor and cognitive deficits seen in the substantial subset of AD patients who harbor concurrent TDP-43 pathology (limbic-predominant age-related TDP-43 encephalopathy, or LATE).

Other TDP-43 Proteinopathies

STMN2 cryptic splicing has also been detected in:

• Inclusion body myopathy: where TDP-43 pathology is found in affected skeletal muscle
• Limbic-predominant age-related TDP-43 encephalopathy (LATE): common in elderly individuals, often co-occurring with AD pathology
• Perry syndrome: a rare disorder featuring TDP-43 inclusions in brainstem neurons

Biomarker Potential

CSF Biomarker

Detection of truncated STMN2 mRNA or cryptic exon-containing transcripts in cerebrospinal fluid (CSF) is under active development as a biomarker for TDP-43 proteinopathies. Unlike [neurofilament light](/biomarkers/neurofilament-light-chain-nfl) chain (NfL), which reflects generalized neurodegeneration, STMN2 cryptic exon products would be specific to TDP-43 dysfunction, enabling:

• Diagnostic specificity: distinguishing TDP-43 proteinopathies from other forms of ALS/FTD (e.g., SOD1-ALS, [tau](/proteins/tau)[/entities/
• Patient stratification: identifying individuals most likely to benefit from STMN2-restoring therapies
• Pharmacodynamic monitoring: tracking target engagement in clinical trials of STMN2-directed therapeutics

Tissue Biomarker

In post-mortem tissue, immunohistochemical detection of truncated stathmin-2 protein provides a sensitive marker of TDP-43 pathology, complementing TDP-43 immunostaining and potentially revealing early-stage pathology before overt TDP-43 inclusions form.

Therapeutic Targeting

• Patient stratification: identifying individuals most likely to benefit from STMN2-restoring therapies
• Pharmacodynamic monitoring: tracking target engagement in clinical trials of STMN2-directed therapeutics

Tissue Biomarker

In post-mortem tissue, immunohistochemical detection of truncated stathmin-2 protein provides a sensitive marker of TDP-43 pathology, complementing TDP-43 immunostaining and potentially revealing early-stage pathology before overt TDP-43 inclusions form.

Therapeutic Targeting

Antisense Oligonucleotides (ASOs) — QRL-201

QRL-201 (Quralis Corporation) is a first-in-class antisense oligonucleotide (ASO) targeting the STMN2 cryptic splice site to restore full-length stathmin-2 expression in patients with ALS. QRL-201 is delivered by intrathecal injection and blocks the cryptic exon inclusion that occurs when TDP-43 is depleted from the nucleus.

ANQUR Clinical Trial (Phase 1/2): The ANQUR study is a double-blind, placebo-controlled clinical trial that has enrolled a total of 69 patients across dose escalation (n=17) and dose range-finding (DRF, n=52) phases:

• First patient dosed: March 2023
• Dose escalation: Completed successfully with favorable safety profile
• DRF phase: First participant dosed in DRF in July 2025
• Safety: The unblinded Data Safety Monitoring Board has consistently recommended the study continue without modification (most recently December 2025)
• Early efficacy signals (February 2026): QRL-201 demonstrated a statistically significant effect on a neurofilament biomarker and an overall trend of slowing disease progression as measured by the ALSFRS-R. Subgroup analysis showed statistically significant effects on ALSFRS-R functional decline
• EU CTA: Clinical Trial Authorisation granted in the European Union for expanded enrollment
• Phase 3 plans: Preparations underway to advance QRL-201 into a pivotal Phase 3 clinical trial projected for 2027

QRL-201 represents the first clinical program in sporadic ALS to show potential restoration of STMN2 expression, combined with evidence of target engagement and signals of disease modification.

Dual-Targeting snRNA Gene Therapy

A gene therapy approach using engineered small nuclear RNAs (snRNAs) has been developed to simultaneously correct cryptic splicing of both STMN2 and UNC13A from a single AAV vector. In iPSC-derived motor neurons with TDP-43 knockdown, dual-targeting snRNAs restored normal STMN2 pre-mRNA processing and rescued stathmin-2 protein levels while also correcting UNC13A splicing. This approach addresses the theoretical limitation of ASOs that target only one cryptic exon, as both STMN2 and UNC13A contribute to motor neuron dysfunction through distinct but complementary mechanisms (axonal maintenance and synaptic transmission, respectively).

CRISPR-dCasRx

The CRISPR effector dCasRx has been used to block STMN2 cryptic splicing in TDP-43-deficient human motor neurons, providing proof-of-concept for RNA-targeted gene therapy. This approach uses catalytically inactive Cas13d to sterically block the cryptic splice site without cleaving the mRNA, preserving the native transcript while preventing aberrant processing.

Gene Therapy — AAV-STMN2

AAV-mediated overexpression of STMN2 is under investigation as an alternative approach to bypass the cryptic splicing defect entirely by providing exogenous stathmin-2 from a delivered transgene. This strategy would restore stathmin-2 regardless of TDP-43 status but requires achieving appropriate expression levels in target motor neurons.

Therapeutic Considerations

Several factors complicate STMN2-directed therapy:

• Timing: Whether stathmin-2 restoration can halt or reverse existing neurodegeneration, or only prevent further decline
• Cell-type specificity: Achieving sufficient stathmin-2 restoration specifically in vulnerable [motor-neurons](/cell-types/motor-neurons) and cortical neurons
• UNC13A synergy: Whether co-targeting STMN2 and UNC13A cryptic exons provides additive or synergistic benefit
• Upstream TDP-43 pathology: STMN2 restoration addresses a downstream consequence but does not correct the underlying TDP-43 mislocalization

Brain Atlas Resources

• Allen Human Brain Atlas: [Stathmin-2 expression search](https://human.brain-map.org/microarray/search/show?search_term=Stathmin-2)
• Allen Mouse Brain Atlas: [Stathmin-2 search](https://mouse.brain-map.org/search/index.html?query=Stathmin-2)
• Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
• BrainSpan Developmental Transcriptome: [Stathmin-2 developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=Stathmin-2)

See Also

• [Proteins Index](/proteins)
• [Axonal Transport Defects](/mechanisms/axonal-transport-defects)
• [Amyotrophic Lateral Sclerosis](/diseases/als)
• [Parkinson's Disease](/diseases/parkinsons-disease)

External Links

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [UniProt: Stathmin-2](https://www.uniprot.org)
• [NCBI Protein: SCG10](https://www.ncbi.nlm.nih.gov)
• [Wikipedia: Stathmin](https://en.wikipedia.org/wiki/Stathmin)

Background

The study of Stathmin 2 (Scg10) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

[@allen]: - [Allen Brain Atlas](https://brain-map.org)
[@allena]: - [Allen Human Brain Atlas: Stathmin-2 search](https://human.brain-map.org/microarray/search/show?search_term=Stathmin-2)
[@allenb]: - [Allen Mouse Brain Atlas: Stathmin-2 search](https://mouse.brain-map.org/search/index.html?query=Stathmin-2)
[@allenc]: - [Allen Cell Type Atlas](https://portal.brain-map.org/atlases-and-data/rnaseq)
[@brainspan]: - [BrainSpan Developmental Transcriptome](https://www.brainspan.org)## See Also
[@stmn]: - stmn2 — Gene encoding stathmin-2
[@tdp]: - tdp-43 — Key regulator of STMN2 splicing
[@tardbp]: - tardbp — Gene encoding TDP-43
[@unca]: - unc13a — Other major TDP-43 cryptic splicing target
[@tdpproteinopathy]: - tdp-43-proteinopathy — Mechanism of TDP-43 pathology
[@als]: - als — Disease where stathmin-2 loss is pathogenic
[@ftd]: - ftd — FTLD-TDP involves STMN2 cryptic splicing
[@motorneurons]: - motor-neurons — Primary cell type expressing stathmin-2
[@nflprotein]: - nfl-protein — Complementary neurodegeneration biomarker## See Also
[@proteins]: - [Proteins Index
[@alzheimers]: - alzheimers
[@parkinsons]: - parkinsons
[@neuroinflammation]: - neuroinflammation
[@uniprot]: - [UniProt: Q93045](https://www.uniprot.org/uniprot/Q93045)
[@genecards]: - [GeneCards: STMN2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=STMN2)
[@clinicaltrialsgov]: - [ClinicalTrials.gov: QRL-201](https://clinicaltrials.gov/search?term=QRL-201)
[@alzforum]: - [ALZFORUM: QRL-201](https://www.alzforum.org/therapeutics/qrl-201)

Pathway Diagram

References

[Klim JR, Williams LA, Limone F, et al., (2019). ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair. Nature Neuroscience, 22(2):167-179. [DOI (2019)](https://doi.org/10.1038/s41593-018-0300-4)

[Melamed Z, et al., (2019). Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration. Nature Neuroscience, 22(2):180-190. [DOI (2019)](https://doi.org/10.1038/s41593-018-0293-z)

[Baughn MW, et al., (2023). Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science, 379(6637):1140-1149. [DOI (2023)](https://doi.org/10.1126/science.abq5622)

[Guerra San Juan I, et al., (2023). SCG10 is required for peripheral axon maintenance and regeneration in mice. J Cell Biol, 222(7):e202206030. [PMID:37283026 (2023)](https://pubmed.ncbi.nlm.nih.gov/37283026/)

[Bhola T, et al., (2025). Stathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin. PNAS, 122(21). [PMID:40392845 (2025)](https://pubmed.ncbi.nlm.nih.gov/40392845/)

[Agra Almeida Quadros AR, et al., (2024). Cryptic splicing of stathmin-2 and UNC13A mRNAs is a pathological hallmark of TDP-43-associated Alzheimer's Disease. Acta Neuropathologica, 147:9. [DOI (2024)](https://doi.org/10.1007/s00401-023-02655-0)

[Krus KL, et al., (2022). Stathmin-2: adding another piece to the puzzle of TDP-43 proteinopathies. JCI, 132(7):e142854. [DOI (2022)](https://doi.org/10.1172/JCI142854)

[Beri S, et al., (2024). Targeting STMN2 for neuroprotection in Spinal Muscular Atrophy. Cell Mol Life Sci, 81:487. [DOI (2024)](https://doi.org/10.1007/s00018-024-05550-3)

Unknown, QurAlis Corporation. (2026). QurAlis demonstrates effects on disease progression and target engagement in ANQUR clinical trial of QRL-201. [Press release (2026)

[Brown AL, et al., (2022). TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A. Nature, 603(7899):131-137. [DOI (2022)](https://doi.org/10.1038/s41586-022-04436-3)

[Ma XR, et al., (2022). TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A. Nature, 603(7899):124-130. [DOI (2022)](https://doi.org/10.1038/s41586-022-04424-7)

[Seddighi S, et al., (2024). Loss of TDP-43 induces synaptic dysfunction that is rescued by UNC13A splice-switching ASOs. J Clin Invest, 134(13):e177567. [DOI (2024)](https://doi.org/10.1172/JCI177567)

[Humphrey J, et al., (2025). Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathies. bioRxiv. [DOI (2025)](https://doi.org/10.1101/2025.12.01.691001)

-, Allen Brain Atlas (n.d.)

-, Allen Human Brain Atlas: Stathmin-2 search (n.d.)

-, Allen Mouse Brain Atlas: Stathmin-2 search (n.d.)

-, Allen Cell Type Atlas (n.d.)

-, BrainSpan Developmental Transcriptome (n.d.)

Unknown, - stmn2 — Gene encoding stathmin-2 (n.d.)

Unknown, - tdp-43 — Key regulator of STMN2 splicing (n.d.)

Unknown, - tardbp — Gene encoding TDP-43 (n.d.)

Unknown, - unc13a — Other major TDP-43 cryptic splicing target (n.d.)

Unknown, - tdp-43-proteinopathy — Mechanism of TDP-43 pathology (n.d.)

Unknown, - als — Disease where stathmin-2 loss is pathogenic (n.d.)

Unknown, - ftd — FTLD-TDP involves STMN2 cryptic splicing (n.d.)

Unknown, - motor-neurons — Primary cell type expressing stathmin-2 (n.d.)

Unknown, - nfl-protein — Complementary neurodegeneration biomarker## See Also (n.d.)

Unknown, - [Proteins Index (n.d.)

Unknown, - alzheimers (n.d.)

Unknown, - parkinsons (n.d.)

Unknown, - neuroinflammation (n.d.)

-, UniProt: Q93045 (n.d.)

-, GeneCards: STMN2 (n.d.)

-, ClinicalTrials.gov: QRL-201 (n.d.)

-, ALZFORUM: QRL-201 (n.d.)

Pathway Diagram

The following diagram shows the key molecular relationships involving Stathmin-2 (SCG10) discovered through SciDEX knowledge graph analysis: