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Vacuolar protein sorting-associated protein 41 subunit of HOPS complex (VPS41)
- Target
- VPS41
- Molecular classification
- Scaffold protein, Vesicle trafficking protein, Homotypic fusion and protein sorting (HOPS) complex subunit, Contains WD40, tetratricopeptide repeat (TPR)-like, Clathrin heavy chain repeat (CHCR), and RING-H2 zinc finger domains
01
Overview
VPS41 is a protein subunit of the HOPS complex, a multisubunit tethering factor required for the fusion of late endosomes and lysosomes. VPS41 contains several domains (including WD40, TPR-like, CHCR, and RING-H2 zinc finger), mediating interactions with Rab7 (Ypt7 in yeast) and other HOPS subunits. Its recruitment and localization are regulated by phosphorylation events and membrane interactions. VPS41 is essential for the correct delivery of endocytic and autophagic cargo to lysosomes, and its dysfunction leads to impaired vesicle fusion, defective autophagic flux, and is implicated in neurodegenerative diseases with abnormal lysosomal function. Knockout models confirm its essential role in development.
- Other names
- Vacuolar protein sorting-associated protein 41VPS41 subunit of HOPS complexVps41HOPS complex subunit Vps41
02
Mechanism of action
For hypothetical/possible future drugs: modulation (activation/inhibition) of VPS41 function may restore lysosomal fusion, autophagy, or trafficking in disease states
03
Biological functions
Lysosomal membrane fusionEndosome-lysosome fusionAutophagy regulationVesicular traffickingRecruitment of HOPS complex to late endosomes
04
Disease associations
Neurodegenerative disease (e.g., mutations associated with ataxia and dystonia)Potential involvement in Parkinson's disease (impaired neuroprotective function against alpha-synuclein aggregates)Lysosomal storage disorders (due to faulty endocytic/autophagic cargo delivery)Other lysosomal dysfunctions
05
Safety considerations
Loss of VPS41 function is embryonically lethal in knockout miceMutations may result in neurodegenerative phenotypesDeficient VPS41 impairs lysosomal/autophagic function, potentially leading to cellular toxicity, accumulation of undigested material, and defective neuronal maintenance
06
Interacting drugs
No clinically approved drugs are directly listed as interacting with VPS41 in current literature. Research is ongoing into molecules modulating vesicular trafficking and lysosome function, but specific drugs directly targeting VPS41 have not been characterized
07
Biomarkers
Genetic variants (mutations in VPS41)Protein expression levels of VPS41 or other HOPS complex componentsDefective lysosomal/autophagic flux markers (e.g., LC3II for autophagy)
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