V-type proton ATPase subunit B, brain isoform

ATP6V1B2 encodes the V-type proton ATPase subunit B, brain isoform, a non-catalytic component of the V1 complex of vacuolar H+-ATPase (UniProt: P21281). This multisubunit enzyme hydrolyzes ATP to translocate protons across membranes, acidifying intracellular compartments and, in some cell types, the extracellular environment. The protein is particularly important in renal intercalated cells for proton secretion under baseline conditions.

UniProt documentation associates ATP6V1B2 mutations with Zimmermann-Laband syndrome 2 and congenital deafness with onychodystrophy, both rare developmental disorders (UniProt: P21281). The gene is expressed broadly in tissues requiring active proton pumping, including neural and epithelial cells.

In Alzheimer's disease, ATP6V1B2 is significantly downregulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.34 across two subcellular fractions (Chaparral AD proteomics). The downregulation was detected in a TMT-labeled proteomics study analyzing four subcellular fractions, suggesting potential impairment of lysosomal and vacuolar acidification pathways relevant to amyloid and tau clearance in Alzheimer's pathology.