VPS13D Protein

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VPS13D Protein

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VPS13D Protein — Vacuolar Protein Sorting 13 Homolog D

Introduction

Vps13D Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">VPS13D Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Vacuolar Protein Sorting 13 Homolog D</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>VPS13D</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q5THJ3](https://www.uniprot.org/uniprot/Q5THJ3)</td></tr>
<tr><td><strong>Function</strong></td><td>Large cytosolic protein involved in membrane trafficking and organelle contact sites</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~500 kDa</td></tr>
<tr><td><strong>Subcellular Location</strong></td><td>Cytosol, endoplasmic reticulum, mitochondria</td></tr>
<tr><td><strong>Protein Family</strong></td><td>VPS13 family (chorein domain proteins)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ms" style="color:#ef9a9a">Ms</a>, <a href="/wiki/parkinson" style="color:#ef9a9a">Parkinson</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">13 edges</a></td>
</tr>
</table>
</div>

Overview

...

VPS13D Protein — Vacuolar Protein Sorting 13 Homolog D

Introduction

Vps13D Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-protein">
<table>
<tr><th colspan="2" style="background:#e8f4f8; text-align:center; font-size:1.1em;">VPS13D Protein</th></tr>
<tr><td><strong>Protein Name</strong></td><td>Vacuolar Protein Sorting 13 Homolog D</td></tr>
<tr><td><strong>Gene Symbol</strong></td><td>VPS13D</td></tr>
<tr><td><strong>UniProt ID</strong></td><td>[Q5THJ3](https://www.uniprot.org/uniprot/Q5THJ3)</td></tr>
<tr><td><strong>Function</strong></td><td>Large cytosolic protein involved in membrane trafficking and organelle contact sites</td></tr>
<tr><td><strong>Molecular Weight</strong></td><td>~500 kDa</td></tr>
<tr><td><strong>Subcellular Location</strong></td><td>Cytosol, endoplasmic reticulum, mitochondria</td></tr>
<tr><td><strong>Protein Family</strong></td><td>VPS13 family (chorein domain proteins)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ms" style="color:#ef9a9a">Ms</a>, <a href="/wiki/parkinson" style="color:#ef9a9a">Parkinson</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">13 edges</a></td>
</tr>
</table>
</div>

Overview

VPS13D (Vacuolar Protein Sorting 13 Homolog D) is a massive (~500 kDa) cytosolic protein that plays essential roles in membrane trafficking, organelle dynamics, and [autophagy](/entities/autophagy)[@rzepnikowska2017]. VPS13 family members (VPS13A-D) are characterized by a unique chorein domain and function as lipid transfer proteins at membrane contact sites between organelles[@kumar2018]. VPS13D is particularly important for mitochondrial quality control, lysosomal function, and cellular metabolism, with mutations causing recessive neurological disorders including cerebellar ataxia and hereditary spastic paraplegia[@ganos2022]. Recent studies have also implicated VPS13D variants in Parkinson's disease risk, highlighting its importance in neurodegeneration[@chia2023].

Molecular Mechanisms

Structure and Domain Organization

VPS13D contains several key structural features[@rzepnikowska2017]:

N-terminal Domain: Mediates protein-protein interactions and membrane association
Chorein Domain: The central domain responsible for lipid transfer activity between membranes
C-terminal Regions: Involved in organelle targeting and regulation

The chorein domain enables VPS13D to shuttle lipids between membrane bilayers at contact sites, facilitating membrane remodeling and lipid homeostasis.

Lipid Transfer at Contact Sites

VPS13D functions at membrane contact sites (MCS) where two organelles come into close proximity (~10-30 nm). At these sites, VPS13D transfers lipids including:

Phosphatidylinositol (PI) and its phosphorylated derivatives (PIP, PIP2, PIP3)
Phosphatidylserine (PS)
Phosphatidylethanolamine (PE)

This lipid transfer activity is crucial for maintaining organelle identity, supporting membrane dynamics, and enabling cellular signaling.

Role in Neurodegeneration

Parkinson's Disease

VPS13D has emerged as a Parkinson's disease risk gene through GWAS and exome sequencing studies[@chia2023]:

Lysosomal Dysfunction: VPS13D is essential for proper lysosomal function. Parkinson's disease is strongly linked to lysosomal dysfunction (GBA, ATP13A2 mutations), and VPS13D variants may contribute to similar pathways.

Mitochondrial Quality Control: VPS13D regulates mitophagy and mitochondrial dynamics. Impaired mitochondrial quality control is a core pathogenic mechanism in PD.

Autophagy Regulation: VPS13D deficiency leads to accumulation of autophagic substrates and impaired autophagic flux, similar to observations in PD brains.

[α-Synuclein](/proteins/alpha-synuclein) Metabolism: VPS13D dysfunction may affect pathways involved in α-synuclein synthesis, aggregation, and clearance.

Spinocerebellar Ataxia and Hereditary Spastic Paraplegia

Biallelic VPS13D mutations cause recessive neurological disorders[@ganos2022]:

Spinocerebellar Ataxia (SCA): Characterized by progressive cerebellar ataxia, dysarthria, and oculomotor abnormalities
Hereditary Spastic Paraplegia (HSP): Characterized by progressive lower limb spasticity and weakness

These disorders involve degeneration of cerebellar and corticospinal tract [neurons](/entities/neurons), highlighting the importance of VPS13D in neuronal survival.

Other Neurodegenerative Diseases

Alzheimer's Disease: Altered VPS13D expression reported in AD brains; may affect [APP](/entities/app-protein) processing and [Aβ](/proteins/amyloid-beta) metabolism through membrane trafficking pathways
Amyotrophic Lateral Sclerosis (ALS): VPS13D variants may modify disease progression through effects on autophagy and mitochondrial function

Therapeutic Implications

VPS13D represents a potential therapeutic target[@chia2023][@liu2024]:

Enhancer Development: Small molecules that enhance VPS13D function could improve lysosomal and mitochondrial function in neurons

Gene Therapy: AAV-mediated VPS13D delivery may benefit patients with loss-of-function mutations

Modulator Screening: High-throughput screens for VPS13D activity modulators could identify novel neuroprotective compounds

Pathway Interactions

VPS13D integrates with multiple cellular pathways:

Mermaid diagram (expand to render)

Key Research Findings

VPS13D loss-of-function causes recessive ataxia and spasticity in humans and mice[@ganos2022]
VPS13D regulates mitochondrial morphology and mitophagy through PINK1/Parkin-independent pathways[@rzepnikowska2017]
GWAS has identified VPS13D variants associated with PD risk in European and East Asian populations[@chia2023]
VPS13D deficiency leads to neurodegeneration in Drosophila models with features of PD[@liu2024]
VPS13D functions at ER-mitochondria contact sites to regulate lipid transfer and mitophagy

Background

The study of Vps13D Protein 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.

External Links

[UniProt: Q5THJ3](https://www.uniprot.org/uniprot/Q5THJ3)
[NCBI Gene: VPS13D](https://www.ncbi.nlm.nih.gov/gene/27127)
[RCSB PDB: VPS13D structure](https://www.rcsb.org/)

References

[Rzepnikowska W, et al, (2017) (2017)](https://pubmed.ncbi.nlm.nih.gov/28263320/))

[Kumar N, et al, (2018) (2018)](https://pubmed.ncbi.nlm.nih.gov/29995854/))

[Ganos C, et al, (2022) (2022)](https://pubmed.ncbi.nlm.nih.gov/34782419/))

[Chia R, et al, (2023) (2023)](https://pubmed.ncbi.nlm.nih.gov/36629384/))

[Liu Y, et al, (2024) (2024)](https://pubmed.ncbi.nlm.nih.gov/38419045/))

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Related Entities

VPS13D

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kg_node_id	VPS13D
entity_type	protein
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source_table	wiki_pages
wiki_page_id	wp-957eefb86fd5
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'proteins-vps13d'}
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📊 Evidence Profile Foundational

Evidence Balance

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📗 Cite This Artifact

VPS13D Protein

VPS13D Protein — Vacuolar Protein Sorting 13 Homolog D

Introduction

Overview

VPS13D Protein — Vacuolar Protein Sorting 13 Homolog D

Introduction

Overview

Molecular Mechanisms

Structure and Domain Organization

Lipid Transfer at Contact Sites

Role in Neurodegeneration

Parkinson's Disease

Spinocerebellar Ataxia and Hereditary Spastic Paraplegia

Other Neurodegenerative Diseases

Therapeutic Implications

Pathway Interactions

Key Research Findings

Background

See Also

External Links

References

💬 Discussion