Vacuolar protein sorting-associated protein 16 homolog

VPS16 (vacuolar protein sorting-associated protein 16 homolog) is a core component of the HOPS and CORVET endosomal tethering complexes involved in vesicle-mediated protein trafficking (UniProt: Q9H269). It functions in Rab5-to-Rab7 endosome conversion and mediates tethering and docking during SNARE-mediated membrane fusion. VPS16 is essential for recruitment of VPS33A and for fusion of endosomes, autophagosomes, and lysosomes, thereby regulating late endocytic, phagocytic, and autophagic trafficking pathways.

Mutations in VPS16 are associated with dystonia 30 (DYT30), an autosomal dominant movement disorder with early onset and variable manifestations including cervical and upper limb involvement; some patients present with neurocognitive impairment (UniProt: Q9H269).

VPS16 is down-regulated in Alzheimer's disease brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log₂ fold-change of −0.28 across one of four subcellular fractions examined in post-mortem human brain by TMT-labeled proteomics. This reduced expression may reflect compromised lysosomal-autophagic clearance pathways relevant to AD pathogenesis.