V-type proton ATPase subunit G 2

ATP6V1G2 encodes V-type proton ATPase subunit G 2, a component of the V1 complex of vacuolar H+-ATPase (V-ATPase). This multisubunit enzyme hydrolyzes ATP to transport protons across membranes, thereby acidifying intracellular compartments and, in some cell types, the extracellular environment (UniProt: O95670).

V-ATPase subunit G 2 functions in pH regulation within endosomal, lysosomal, and other acidic cellular compartments. These organelles are critical for protein degradation, autophagy, and cellular homeostasis—processes fundamental to neuronal health. The protein is expressed broadly across tissues and has no documented Mendelian disease associations in UniProt.

In Alzheimer's disease, ATP6V1G2 is significantly downregulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.49 across subcellular fractions (Chaparral AD proteomics). This reduction may impair lysosomal and endosomal acidification, potentially compromising autophagic clearance of amyloid-β and tau aggregates—hallmark pathologies in AD pathogenesis.