V-type proton ATPase catalytic subunit A

ATP6V1A (V-type proton ATPase catalytic subunit A) is the catalytic component of vacuolar H+-ATPase (V-ATPase), a multisubunit enzyme that hydrolyzes ATP to pump protons across intracellular membranes and maintain compartment acidification (UniProt: P38606). The protein also regulates intracellular iron homeostasis and may support neurite development and synaptic connectivity. Beyond its housekeeping roles, ATP6V1A participates in viral membrane fusion events during Rabies virus infection (UniProt: P38606).

ATP6V1A is ubiquitously expressed and particularly relevant in neurons, where V-ATPase dysfunction has been linked to infantile epileptic encephalopathy (IECEE3) and cutis laxa autosomal recessive type 2D (ARCL2D), a neurodevelopmental disorder with seizures and hypotonia (UniProt: P38606).

In Alzheimer's disease, ATP6V1A is consistently down-regulated in post-mortem AD brain compared to age-matched controls (mean log2 fold-change −0.32 across two subcellular fractions), suggesting impaired lysosomal and endosomal acidification may contribute to AD pathophysiology (Chaparral AD proteomics).