Vacuolar protein sorting-associated protein 18 homolog

VPS18 (vacuolar protein sorting-associated protein 18 homolog) is a 973-amino-acid protein that functions in vesicle-mediated protein trafficking to lysosomal compartments (UniProt: Q9P253). It serves as a core component of the HOPS and CORVET endosomal tethering complexes, which regulate the conversion of early endosomes to late endosomes and mediate membrane fusion during endocytic, autophagic, and phagocytic pathways. VPS18 is required for fusion of endosomes and autophagosomes with lysosomes and is also involved in dendrite development.

VPS18 is broadly relevant to neuronal homeostasis through its roles in autophagy and endosomal-lysosomal trafficking, processes critical for neuronal protein quality control and organelle turnover. No disease associations are annotated in UniProt for this protein.

VPS18 shows decreased abundance in Alzheimer's disease brain tissue. Chaparral AD proteomics analysis of post-mortem AD brain compared to age-matched controls identified VPS18 as downregulated (mean log2 fold-change: −0.31) in one subcellular fraction, suggesting reduced lysosomal and autophagic trafficking capacity in the AD brain—a pattern consistent with impaired cellular protein clearance mechanisms implicated in neurodegeneration.