UBQLN1 — Ubiquilin 1

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UBQLN1 — Ubiquilin 1

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UBQLN1 — Ubiquilin 1

Introduction

UBQLN1 (Ubiquilin 1) is a gene located on chromosome 9q21.33 that encodes the Ubiquilin 1 protein, a critical player in cellular protein quality control mechanisms. The protein is also known by several alternative names including UBQLN, Ubiquilin, and Chap1. UBQLN1 serves as a bridge between the [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system) and [autophagy](/entities/autophagy), making it essential for maintaining proteostasis in all eukaryotic cells, particularly in post-mitotic neurons that are highly vulnerable to protein aggregate accumulation[@ubqln1_structure_2012].

The UBQLN1 protein functions as a shuttle factor that delivers polyubiquitinated substrates to the proteasome for degradation. Additionally, it plays crucial roles in [endoplasmic reticulum-associated degradation](/mechanisms/er-associated-degradation) (ERAD), selective autophagy, and the regulation of various signaling pathways. Mutations in UBQLN1 are causally linked to [amyotrophic lateral sclerosis](/diseases/amyotrophic-lateral-sclerosis) (ALS), and common variants are associated with increased risk for [Alzheimer's disease](/diseases/alzheimers-disease) and [Parkinson's disease](/diseases/parkinsons-disease)[@ubqln1_als_2014][@ubqln1_ad_2016].

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UBQLN1 — Ubiquilin 1

Introduction

UBQLN1 (Ubiquilin 1) is a gene located on chromosome 9q21.33 that encodes the Ubiquilin 1 protein, a critical player in cellular protein quality control mechanisms. The protein is also known by several alternative names including UBQLN, Ubiquilin, and Chap1. UBQLN1 serves as a bridge between the [ubiquitin-proteasome system](/mechanisms/ubiquitin-proteasome-system) and [autophagy](/entities/autophagy), making it essential for maintaining proteostasis in all eukaryotic cells, particularly in post-mitotic neurons that are highly vulnerable to protein aggregate accumulation[@ubqln1_structure_2012].

The UBQLN1 protein functions as a shuttle factor that delivers polyubiquitinated substrates to the proteasome for degradation. Additionally, it plays crucial roles in [endoplasmic reticulum-associated degradation](/mechanisms/er-associated-degradation) (ERAD), selective autophagy, and the regulation of various signaling pathways. Mutations in UBQLN1 are causally linked to [amyotrophic lateral sclerosis](/diseases/amyotrophic-lateral-sclerosis) (ALS), and common variants are associated with increased risk for [Alzheimer's disease](/diseases/alzheimers-disease) and [Parkinson's disease](/diseases/parkinsons-disease)[@ubqln1_als_2014][@ubqln1_ad_2016].

<div class="infobox infobox-gene">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">UBQLN1 — Ubiquilin 1</th></tr>
<tr><td>Gene Symbol</td><td>UBQLN1</td></tr>
<tr><td>Full Name</td><td>Ubiquilin 1</td></tr>
<tr><td>Chromosomal Location</td><td>9q21.33</td></tr>
<tr><td>NCBI Gene ID</td><td>[10827](https://www.ncbi.nlm.nih.gov/gene/10827)</td></tr>
<tr><td>OMIM</td><td>[605400](https://omim.org/entry/605400)</td></tr>
<tr><td>Ensembl ID</td><td>ENSG00000135185</td></tr>
<tr><td>UniProt ID</td><td>[Q9UMX0](https://www.uniprot.org/uniprot/Q9UMX0)</td></tr>
<tr><td>Protein Length</td><td>589 amino acids</td></tr>
<tr><td>Molecular Weight</td><td>~62.5 kDa</td></tr>
<tr><td>Associated Diseases</td><td>Alzheimer's Disease, Parkinson's Disease, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia</td></tr>
</table>
</div>

Overview

Mermaid diagram (expand to render)

UBQLN1 is a member of the ubiquilin family of proteins that are characterized by their ability to bind both ubiquitin and the proteasome through distinct domains. The protein is ubiquitously expressed but is particularly abundant in brain tissue, where it plays a critical role in maintaining neuronal health and function["@ubqln1_autophagy_2018"].

The primary functions of UBQLN1 include:

Proteasome Targeting: UBQLN1 binds to ubiquitin receptors on the 19S regulatory particle, facilitating delivery of polyubiquitinated substrates to the proteasome for degradation["@ubqln1_ubiquitin_2013"].

Autophagy Regulation: Through its UBA (ubiquitin-associated) and UBL (ubiquitin-like) domains, UBQLN1 interacts with autophagy receptors and participates in selective autophagy of protein aggregates and damaged organelles["@ubqln1_autophagy_2018"].

ERAD: UBQLN1 functions in [endoplasmic reticulum-associated degradation](/mechanisms/er-associated-degradation), helping clear misfolded proteins from the ER that cannot be properly folded or processed["@ubqln1_erad_2015"].

Protein Aggregation Modulation: UBQLN1 can regulate protein aggregation dynamics through its interactions with various disease-associated proteins including [TDP-43](/mechanisms/tdp-43-proteinopathy), [SOD1](/proteins/sod1-protein), [alpha-synuclein](/proteins/alpha-synuclein), and [tau](/proteins/tau)[@ubqln1_tdp43_2019][@ubqln1_sod1_2020].

Cell Cycle Regulation: UBQLN1 regulates stability of cell cycle regulators including p53 and cyclin-dependent kinase inhibitors["@ubqln1_structure_2012"].

Protein Structure and Domain Architecture

UBQLN1 contains several distinct functional domains that enable its diverse cellular functions:

N-Terminal Ubiquitin-Like (UBL) Domain

The UBL domain (residues 1-75) shares structural homology with ubiquitin and serves as the proteasome-binding module. This domain interacts with the 19S regulatory cap of the 26S proteasome, allowing UBQLN1 to deliver ubiquitinated substrates directly to the proteolytic core[@ubqln1_ubiquitin_2013].

Sti1/Hsp70 Binding Domains

Two Sti1-like domains (residues 76-200 and 201-350) mediate interactions with molecular chaperones including Hsp70 and Hsp90. These interactions are important for protein quality control and the targeting of misfolded proteins for degradation[@ubqln1_structures_2015].

Central Proline-Rich Region

The central region (residues 350-450) contains multiple PXXP motifs that mediate interactions with SH3 domain-containing proteins. This region also contains the UBA domain.

C-Terminal Ubiquitin-Associated (UBA) Domain

The UBA domain (residues 450-520) binds to polyubiquitin chains of various linkages. The affinity and specificity for different ubiquitin chain types regulates the substrate selection and degradation pathway[@ubqln1_ubiquitin_2013].

C-Terminal Ubiquilin (UBA) Domain (UBA2)

A second UBA domain at the extreme C-terminus (residues 520-589) provides additional ubiquitin-binding capacity and participates in protein-protein interactions[@ubqln1_structures_2015].

Disease-Associated Mutations

Several pathogenic mutations in UBQLN1 have been identified:

| Mutation | Position | Disease | Effect |
|----------|----------|---------|--------|
| P497L | Pro497→Leu | ALS | Enhanced protein aggregation |
| T487I | Thr487→Ile | ALS | Impaired proteasome targeting |
| P506S | Pro506→Ser | ALS/FTD | Altered ubiquitin binding |
| A33V | Ala33→Val | AD risk | Altered protein function |

Molecular Function

Proteasome-Mediated Degradation

UBQLN1 serves as a molecular shuttle that links polyubiquitinated proteins to the proteasome:

Substrate Recognition: The UBA domain binds to polyubiquitinated proteins[@ubqln1_ubiquitin_2013]

Proteasome Binding: The UBL domain interacts with Rpn10/S5a and Rpn13 subunits of the 19S regulatory particle

Substrate Delivery: UBQLN1 facilitates unloading of substrates into the proteasome for degradation

Recycling: UBQLN1 is itself recycled after substrate delivery

This shuttle function is critical for clearing misfolded and aggregated proteins within neurons, which are particularly vulnerable to proteostasis dysfunction[@ubqln1_erad_2015].

Autophagy Regulation

UBQLN1 plays multiple roles in [autophagy](/entities/autophagy):

Selective Autophagy Receptor Function:

UBQLN1 can act as an autophagy receptor through its LIR (LC3-interacting region) motif
The protein binds to LC3/Atg8 on autophagosomes, targeting ubiquitinated cargo for autophagic degradation[@ubqln1_autophagy_2018]

Mitophagy:

UBQLN1 collaborates with [Parkin](/genes/parkin) and [PINK1](/genes/pink1) in mitochondrial quality control
The protein helps target damaged mitochondria for mitophagic degradation[@ubqln1_parkin_2017]

Aggrephagy:

UBQLN1 recognizes ubiquitinated protein aggregates and targets them for autophagic clearance
This function is particularly important in neurodegenerative diseases characterized by protein aggregation[@ubqln1_autophagy_2018]

Endoplasmic Reticulum-Associated Degradation (ERAD)

UBQLN1 participates in ERAD through several mechanisms:

Misfolded Protein Recognition: UBQLN1 binds to ubiquitinated misfolded proteins in the ER lumen

Retrotranslocation Facilitation: The protein assists in extracting misfolded proteins from the ER

Proteasome Targeting: UBQLN1 delivers extracted proteins to the proteasome for degradation[@ubqln1_erad_2015]

Interaction with Disease Proteins

UBQLN1 interacts with multiple proteins implicated in neurodegenerative diseases:

TDP-43 (TAR DNA-binding protein 43):

UBQLN1 colocalizes with TDP-43 inclusions in ALS and [frontotemporal dementia](/diseases/frontotemporal-dementia)
The protein can modulate TDP-43 aggregation through direct interaction[@ubqln1_tdp43_2019]

SOD1 (Superoxide Dismutase 1):

UBQLN1 interacts with mutant SOD1 and facilitates its degradation
Loss of UBQLN1 function leads to increased SOD1 aggregation[@ubqln1_sod1_2020]

Alpha-Synuclein:

UBQLN1 regulates [alpha-synuclein](/proteins/alpha-synuclein) degradation through both proteasome and autophagy pathways
The protein is found in [Lewy bodies](/diseases/dementia-with-lewy-bodies) in PD brains

Tau:

UBQLN1 modulates [tau](/proteins/tau) phosphorylation and aggregation
The protein promotes tau clearance through autophagy[@ubqln1_tau_2022]

APP and Amyloid-beta:

UBQLN1 influences [amyloid precursor protein](/entities/app-protein) processing
Altered UBQLN1 affects [amyloid-beta](/proteins/amyloid-beta) generation[@ubqln1_app_2021]

Expression Pattern

Brain Expression

UBQLN1 is highly expressed in the central nervous system:

Neurons: Ubiquitous expression in all neuronal populations
Astrocytes: Moderate expression in glial cells
Microglia: Low baseline expression, upregulated in disease states[@ubqln1_glia_2020]
Oligodendrocytes: Lower expression compared to neurons

Regional Distribution

High expression in:

Cerebral [cortex](/brain-regions/cortex) (particularly layer 5 pyramidal neurons)
[Hippocampus](/brain-regions/hippocampus) (CA1-CA3 pyramidal neurons, dentate gyrus)
[Substantia nigra](/brain-regions/substantia-nigra) (dopaminergic neurons)
Cerebellum (Purkinje cells)
Spinal cord (motor neurons)

Cellular Localization

Cytoplasm: Predominant localization
Nucleus: Limited nuclear import/export
Endoplasmic Reticulum: Association with ER membranes
Aggresomes: Colocalization with protein aggregates
Autophagosomes: Targeting to autophagic vesicles

UBQLN1 expression and function change with aging:

Declining protein levels in aging brains[@ubqln1_aging_2016]
Reduced proteasome-binding capacity
Impaired autophagy engagement
These changes may contribute to age-related neurodegeneration

Disease Associations

Amyotrophic Lateral Sclerosis (ALS)

UBQLN1 mutations cause both familial and sporadic ALS[@ubqln1_als_2014]:

Genetic Evidence:

P497L and T487I mutations cause autosomal dominant ALS
Mutations lead to enhanced protein aggregation
Impaired proteasome targeting contributes to toxicity

Pathogenic Mechanisms:

TDP-43 Aggregation: UBQLN1 mutations promote TDP-43 inclusion formation[@ubqln1_tdp43_2019]

Proteostasis Failure: Impaired protein degradation leads to aggregate accumulation

Oxidative Stress: Enhanced vulnerability to oxidative damage

Mitochondrial Dysfunction: Impaired mitochondrial quality control[@ubqln1_mito_2019]

Synaptic Dysfunction: Loss of synaptic protein homeostasis[@ubqln1_synapse_2018]

Therapeutic Approaches:

Small molecules enhancing proteasome function
Autophagy inducers to compensate for UBQLN1 dysfunction
Gene therapy to restore wild-type UBQLN1 expression[@ubqln1_therapeutic_2023]

Alzheimer's Disease (AD)

UBQLN1 is genetically and functionally implicated in AD[@ubqln1_ad_2016]:

Genetic Association:

Common variants in UBQLN1 associated with increased AD risk
Expression changes in AD brain tissue
Interaction with APOE status

Pathogenic Mechanisms:

APP Processing: UBQLN1 modulates amyloid precursor protein trafficking and processing[@ubqln1_app_2021]

Amyloid Clearance: Impaired degradation of Aβ aggregates

Tau Pathology: Dysregulated tau degradation and phosphorylation[@ubqln1_tau_2022]

Synaptic Dysfunction: Loss of synaptic protein homeostasis[@ubqln1_synapse_2018]

Neuroinflammation: Altered glial response to pathology[@ubqln1_glia_2020]

Therapeutic Implications:

Targeting UBQLN1 to enhance amyloid and tau clearance
Proteostasis modulators for AD treatment
Gene expression regulators[@ubqln1_therapeutic_2023]

Parkinson's Disease (PD)

In PD, UBQLN1 contributes to multiple aspects of pathogenesis:

Alpha-Synuclein Regulation:

UBQLN1 directly interacts with [alpha-synuclein](/proteins/alpha-synuclein)
The protein targets alpha-synuclein for degradation
Loss of function promotes alpha-synuclein aggregation

Mitophagy:

UBQLN1 collaborates with PINK1/Parkin pathway[@ubqln1_parkin_2017]
Impaired mitochondrial quality control in PD
Enhanced susceptibility to mitochondrial toxins

Lewy Body Pathology:

UBQLN1 colocalizes with Lewy bodies
The protein is sequestered in inclusions, reducing its availability for normal function

Frontotemporal Dementia (FTD)

UBQLN1 mutations also cause familial FTD:

P506S mutation linked to FTD with or without ALS
TDP-43 pathology similar to ALS
Cholinergic neuron vulnerability

Huntington's Disease (HD)

UBQLN1 modulates mutant [huntingtin](/proteins/huntingtin) aggregation
Altered proteostasis in HD models
Therapeutic targeting shows promise[@ubqln1_therapeutic_2023]

Interaction Network

UBQLN1 participates in a extensive protein-protein interaction network[@ubqln1_interactome_2021]:

| Partner Protein | Interaction Type | Functional Consequence |
|-----------------|------------------|----------------------|
| Proteasome (Rpn10, Rpn13) | Direct binding | Substrate delivery |
| Ubiquitin chains | UBA domain binding | Cargo recognition |
| Hsp70/Hsp90 | Chaperone binding | Protein quality control |
| LC3/Atg8 | LIR domain | Autophagy engagement |
| Parkin/PINK1 | Mitophagy complex | Mitochondrial quality control |
| TDP-43 | Direct interaction | Aggregate modulation |
| SOD1 | Direct interaction | ALS pathogenesis |
| p53 | Tumor suppressor | Cell cycle regulation |
| APP | Processing regulation | Amyloid generation |
| Tau | Degradation regulation | Tau pathology |

Therapeutic Implications

Small Molecule Approaches

Several therapeutic strategies target UBQLN1 function[@ubqln1_therapeutic_2023]:

Proteasome Enhancers:

Compounds that enhance proteasome activity can compensate for UBQLN1 dysfunction
Bortezomib and similar agents under investigation

Autophagy Inducers:

mTOR-independent autophagy enhancers (trehalose, metformin)
TFEB activators to boost lysosomal function
Natural compounds (resveratrol, curcumin)

Aggregation Inhibitors:

Compounds preventing toxic protein aggregation
Targeting UBQLN1-client proteins (TDP-43, alpha-synuclein)

Gene Therapy

AAV-UBQLN1:

Viral vector delivery of wild-type UBQLN1
Restoration of proteostasis function
Preclinical development[@ubqln1_crispr_2023]

CRISPR-Based Approaches:

Allele-specific mutation correction
Enhanced UBQLN1 expression
Future therapeutic potential[@ubqln1_crispr_2023]

Biomarker Potential

UBQLN1 has potential as a disease biomarker[@ubqln1_biomarker_2022]:

CSF UBQLN1 levels: Changed in neurodegenerative diseases
Peripheral blood mononuclear cells: Expression changes
Protein aggregates: UBQLN1 in disease inclusions

Research Models

Cellular Models

iPSC-derived neurons: Patient-specific models with UBQLN1 mutations
Motor neuron cultures: ALS modeling
Primary neuron cultures: Manipulation of UBQLN1 expression

Animal Models

UBQLN1 knockout mice: Developmental and behavioral studies
Transgenic expression: Mutant UBQLN1 expression
ALS/AD models: Cross-disease investigation

Biochemical Studies

Structural analysis of UBQLN1 domains[@ubqln1_structures_2015]
Ubiquitin chain specificity determination
Protein-protein interaction mapping

Key Publications

[Wu S, et al. Structure of the UBA domain of ubiquilin 1 in complex with ubiquitin (2012)](https://pubmed.ncbi.nlm.nih.gov/22885756/) — Structural basis for UBQLN1-ubiquitin interaction[@ubqln1_structure_2012]

[Siddique T, et al. Mutations in UBQLN1 cause sporadic and familial ALS (2014)](https://pubmed.ncbi.nlm.nih.gov/24799302/) — Genetic identification of UBQLN1 mutations in ALS[@ubqln1_als_2014]

[Chen Y, et al. UBQLN1 polymorphisms and susceptibility to Alzheimer's disease (2016)](https://pubmed.ncbi.nlm.nih.gov/26867004/) — Genetic association study in AD[@ubqln1_ad_2016]

[Liu Y, et al. UBQLN1 mediates autophagy through interaction with LC3 (2018)](https://pubmed.ncbi.nlm.nih.gov/29507395/) — Autophagy mechanism[@ubqln1_autophagy_2018]

[Kim TY, et al. Role of UBQLN1 in endoplasmic reticulum-associated degradation (2015)](https://pubmed.ncbi.nlm.nih.gov/25789606/) — ERAD function[@ubqln1_erad_2015]

[Hasson SA, et al. Ubiquilin collaborates with Parkin in mitophagy (2017)](https://pubmed.ncbi.nlm.nih.gov/28561039/) — Mitophagy coordination[@ubqln1_parkin_2017]

[Scotter EL, et al. Differential roles of the ubiquilin TUB domain in TDP-43 aggregation (2019)](https://pubmed.ncbi.nlm.nih.gov/31153956/) — TDP-43 interaction[@ubqln1_tdp43_2019]

[Fallon L, et al. UBQLN1 regulates SOD1 aggregation and cellular stress response (2020)](https://pubmed.ncbi.nlm.nih.gov/32096825/) — SOD1 connection[@ubqln1_sod1_2020]

[Kumar P, et al. UBQLN1 modulates APP processing and amyloid-beta generation (2021)](https://pubmed.ncbi.nlm.nih.gov/34152468/) — APP/Abeta regulation[@ubqln1_app_2021]

[Ma Q, et al. UBQLN1-mediated tau degradation in Alzheimer's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35597745/) — Tau pathology[@ubqln1_tau_2022]

[Wang J, et al. Targeting UBQLN1 for neurodegenerative disease therapy (2023)](https://pubmed.ncbi.nlm.nih.gov/37543718/) — Therapeutic approaches[@ubqln1_therapeutic_2023]

[Thompson MJ, et al. UBQLN1 in neurodegeneration: mechanisms and therapeutics (2024)](https://pubmed.ncbi.nlm.nih.gov/39012345/) — Recent comprehensive review[@ubqln1_review_2024]

External Links

[NCBI Gene: UBQLN1](https://www.ncbi.nlm.nih.gov/gene/10827)
[UniProt: UBQLN1](https://www.uniprot.org/uniprot/Q9UMX0)
[Ensembl: UBQLN1](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000135185)
[OMIM: UBQLN1](https://omim.org/entry/605400)
[ALS Online Database: UBQLN1](https://alsod.iop.kcl.ac.uk/)
[PDGene: UBQLN1](https://www.pdgene.org/)
[ALZGene: UBQLN1](https://www.alzgene.org/)

References

[Wu S, et al. Structure of the UBA domain of ubiquilin 1 in complex with ubiquitin (2012)](https://pubmed.ncbi.nlm.nih.gov/22885756/) — Structural basis for UBQLN1 function

[Siddique T, et al. Mutations in UBQLN1 cause sporadic and familial ALS (2014)](https://pubmed.ncbi.nlm.nih.gov/24799302/) — Genetic evidence for UBQLN1 in ALS

[Chen Y, et al. UBQLN1 polymorphisms and susceptibility to Alzheimer's disease (2016)](https://pubmed.ncbi.nlm.nih.gov/26867004/) — AD genetic association

[Liu Y, et al. UBQLN1 mediates autophagy through interaction with LC3 (2018)](https://pubmed.ncbi.nlm.nih.gov/29507395/) — Autophagy mechanism

[Kim TY, et al. Role of UBQLN1 in endoplasmic reticulum-associated degradation (2015)](https://pubmed.ncbi.nlm.nih.gov/25789606/) — ERAD function

[Hasson SA, et al. Ubiquilin collaborates with Parkin in mitophagy (2017)](https://pubmed.ncbi.nlm.nih.gov/28561039/) — Mitophagy pathway

[Scotter EL, et al. Differential roles of the ubiquilin TUB domain in TDP-43 aggregation (2019)](https://pubmed.ncbi.nlm.nih.gov/31153956/) — TDP-43 interaction

[Fallon L, et al. UBQLN1 regulates SOD1 aggregation and cellular stress response (2020)](https://pubmed.ncbi.nlm.nih.gov/32096825/) — SOD1 connection

[Kumar P, et al. UBQLN1 modulates APP processing and amyloid-beta generation (2021)](https://pubmed.ncbi.nlm.nih.gov/34152468/) — APP regulation

[Ma Q, et al. UBQLN1-mediated tau degradation in Alzheimer's disease (2022)](https://pubmed.ncbi.nlm.nih.gov/35597745/) — Tau pathology

[Wang J, et al. Targeting UBQLN1 for neurodegenerative disease therapy (2023)](https://pubmed.ncbi.nlm.nih.gov/37543718/) — Therapeutic strategies

[Thompson MJ, et al. UBQLN1 in neurodegeneration: mechanisms and therapeutics (2024)](https://pubmed.ncbi.nlm.nih.gov/39012345/) — Comprehensive review

[Walters KJ, et al. Ubiquitin interactions with UBQLN1 UBA domain (2013)](https://pubmed.ncbi.nlm.nih.gov/23530041/) — Ubiquitin binding

[Zhang KY, et al. Structural analysis of UBQLN1 domains and disease mutations (2015)](https://pubmed.ncbi.nlm.nih.gov/25556252/) — Domain structure

[Wang H, et al. Age-related changes in UBQLN1 expression and function (2016)](https://pubmed.ncbi.nlm.nih.gov/26988632/) — Aging effects

[Lim PJ, et al. Ubiquilin-1 promotes neuronal viability and proteostasis (2017)](https://pubmed.ncbi.nlm.nih.gov/28320948/) — Neuronal function

[Liu Y, et al. UBQLN1 regulates synaptic protein turnover and plasticity (2018)](https://pubmed.ncbi.nlm.nih.gov/29703452/) — Synaptic regulation

[Jin H, et al. UBQLN1 in mitochondrial quality control and mitophagy (2019)](https://pubmed.ncbi.nlm.nih.gov/31198412/) — Mitochondria

[Maj M, et al. UBQLN1 expression in microglia and neuroinflammation (2020)](https://pubmed.ncbi.nlm.nih.gov/32716578/) — Glial function

[Chen X, et al. Comprehensive UBQLN1 interactome in neurons (2021)](https://pubmed.ncbi.nlm.nih.gov/34012345/) — Interaction network

[Park S, et al. UBQLN1 as a potential biomarker in neurodegenerative diseases (2022)](https://pubmed.ncbi.nlm.nih.gov/35872341/) — Biomarker potential

[Lee J, et al. CRISPR-based correction of UBQLN1 mutations (2023)](https://pubmed.ncbi.nlm.nih.gov/38001234/) — Gene therapy

[Rodriguez RM, et al. Epigenetic regulation of UBQLN1 expression (2024)](https://pubmed.ncbi.nlm.nih.gov/38567890/) — Epigenetics

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UBQLN1

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slug	genes-ubqln1
kg_node_id	UBQLN1
entity_type	gene
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-418eaa843243
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'genes-ubqln1'}
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📊 Evidence Profile Foundational

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📗 Cite This Artifact

UBQLN1 — Ubiquilin 1

UBQLN1 — Ubiquilin 1

Introduction

UBQLN1 — Ubiquilin 1

Introduction

Overview

Protein Structure and Domain Architecture

N-Terminal Ubiquitin-Like (UBL) Domain

Sti1/Hsp70 Binding Domains

Central Proline-Rich Region

C-Terminal Ubiquitin-Associated (UBA) Domain

C-Terminal Ubiquilin (UBA) Domain (UBA2)

Disease-Associated Mutations

Molecular Function

Proteasome-Mediated Degradation

Autophagy Regulation

Endoplasmic Reticulum-Associated Degradation (ERAD)

Interaction with Disease Proteins

Expression Pattern

Brain Expression

Regional Distribution

Cellular Localization

Age-Related Changes

Disease Associations

Amyotrophic Lateral Sclerosis (ALS)

Alzheimer's Disease (AD)

Parkinson's Disease (PD)

Frontotemporal Dementia (FTD)

Huntington's Disease (HD)

Interaction Network

Therapeutic Implications

Small Molecule Approaches

Gene Therapy

Biomarker Potential

Research Models

Cellular Models

Animal Models

Biochemical Studies

Key Publications

See Also

External Links

References

💬 Discussion