V-type proton ATPase subunit d 1

ATP6V0D1 encodes the V-type proton ATPase subunit d1, a core component of the vacuolar H+-ATPase (V-ATPase) V0 membrane complex (UniProt: P61421). This multisubunit enzyme hydrolyzes ATP to pump protons across intracellular compartments and, in specialized cells, across the plasma membrane. Beyond acidification, ATP6V0D1 participates in intracellular iron homeostasis by regulating prolyl hydroxylase activity, influences HIF1A stability, and may support cilium assembly through protein trafficking regulation.

V-ATPase functions broadly in endosomal and lysosomal acidification, processes essential for cellular homeostasis and protein degradation pathways. The UniProt record lists no primary disease associations, though V-ATPase dysfunction has been implicated in lysosomal storage and neurodegenerative contexts.

In Alzheimer's disease, ATP6V0D1 is downregulated in human post-mortem brain tissue compared to age-matched controls (Chaparral AD proteomics, mean log2 fold-change −0.63). This reduction may impair lysosomal acidification and clearance of amyloid-β and tau aggregates, processes central to AD pathogenesis, though the modest effect size and detection in a single subcellular fraction warrant further validation across independent AD cohorts.