VPS41 is a core component of the HOPS (homotypic fusion and protein sorting) complex that mediates vesicle trafficking to lysosomes. Primary function: VPS41 facilitates autophagosome-lysosome fusion 1 and endosome-lysosome fusion through SNARE complex assembly 1. It recruits LAMP-positive biosynthetic vesicles from the trans-Golgi network via interaction with Arl8b 2, linking endosomal Rab7 and lysosomal membranes to enable compartment fusion 3. Mechanism: VPS41 interacts with Rab7 and promotes Rab7-HOPS complex association 1, facilitating autophagosome maturation 4. It also functions independently of HOPS in regulated secretion 5. Disease relevance: Compound heterozygous VPS41 mutations cause autosomal recessive spinocerebellar ataxia-29, characterized by impaired HOPS-mediated lysosomal fusion, cytosolic mTORC1 redistribution, and dysregulated TFEB/TFE3 signaling 5. Clinical significance: VPS41 dysregulation affects autophagic cargo clearance and mTORC1-dependent transcriptional control of lysosomal genes. Therapeutic modulation of VPS41 may enhance autophagy in neurodegeneration or restore lysosomal function in disease contexts 1.