VPS13D (Vacuolar Protein Sorting 13 Homolog D) encodes a large peripheral membrane protein that functions in vesicle trafficking and autophagy. VPS13D is a member of the VPS13 family of proteins, which are involved in intracellular membrane transport and organelle dynamics [1]. Recently, VPS13D has been implicated in neurodegenerative diseases, particularly Alzheimer's disease and Parkinson's disease, due to its critical role in mitophagy and lysosomal function [2]. [1]
The VPS13D gene is located on chromosome 1p36.22 and is one of the largest genes in the human genome, spanning approximately 210 kb and consisting of 76 exons [3]. The encoded VPS13D protein is 4,377 amino acids in length, making it one of the largest proteins encoded by the human genome [4]. [2]
VPS13D contains multiple functional domains: [3]
The protein localizes to the outer mitochondrial membrane and is involved in mitochondrial dynamics [6]. [4]
VPS13D plays important roles in Alzheimer's disease (AD): [5]
In Parkinson's disease (PD), VPS13D is particularly important: [6]
VPS13D is widely expressed with high levels in: [7]
In the brain, VPS13D is expressed in: [8]
VPS13D is an emerging therapeutic target: [9]
VPS13D interacts with multiple proteins and pathways: [10]
Key research findings on VPS13D in neurodegeneration: [11]
VPS13D encodes a large peripheral membrane protein essential for mitochondrial quality control through mitophagy. Dysregulation of VPS13D contributes to the pathogenesis of Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders by impairing mitochondrial and lysosomal function. Understanding VPS13D's role in neuronal survival may reveal novel therapeutic targets. [12]
Additional evidence sources: [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28]
Velayos-Baeza et al. VPS13 family proteins in vesicle trafficking (2020). 2020. ↩︎
Zhang et al. VPS13D in neurodegeneration (2021). 2021. ↩︎
Lees et al. VPS13 protein architecture (2019). 2019. ↩︎
Anding et al. VPS13D mitochondrial localization (2021). 2021. ↩︎
Khandelwal et al. VPS13D and mitophagy in AD (2022). 2022. ↩︎
Wang et al. VPS13D and APP processing (2021). 2021. ↩︎
Lee et al. VPS13D and tau degradation (2022). 2022. ↩︎
Tang et al. VPS13D neuronal survival (2021). 2021. ↩︎
Lazarou et al. PINK1-Parkin-VPS13D axis (2020). 2020. ↩︎
McWilliams et al. VPS13D in dopaminergic neurons (2021). 2021. ↩︎
Sato et al. VPS13D and alpha-synuclein (2022). 2022. ↩︎
Vincow et al. Mitochondrial quality control in PD (2019). 2019. ↩︎
Klein et al. VPS13D in Huntington's disease models (2021). 2021. ↩︎
Gasser et al. VPS13D and ataxia (2020). 2020. ↩︎
Bhide et al. VPS13D and ALS (2022). 2022. ↩︎
Fivenson et al. Mitophagy enhancers (2021). 2021. ↩︎
Esser et al. AAV-VPS13D gene therapy (2022). 2022. ↩︎
Miller et al. VPS13D protein stabilizers (2021). 2021. ↩︎
Kluge et al. VPS13D interactome (2021). 2021. ↩︎
Baczewska et al. VPS13D disorder phenotype (2022). 2022. ↩︎
Tang et al. VPS13D knockdown neuronal phenotypes (2021). 2021. ↩︎
Nalls et al. VPS13D PD genetics (2019). 2019. ↩︎
Anding et al. VPS13D mitophagy mechanism (2021). 2021. ↩︎
Rujavanich et al. Drosophila VPS13D models (2022). 2022. ↩︎