ATP6V0A2 encodes the V0a2 subunit of vacuolar H+-ATPase (V-ATPase), a multisubunit proton pump essential for acidifying intracellular compartments 1. As an integral membrane component of the V0 domain, ATP6V0A2 functions in proton translocation across vesicular membranes, maintaining pH homeostasis in the trans-Golgi network, endosomes, and lysosomes 1. Loss of ATP6V0A2 function elevates trans-Golgi pH from normal (5.80) to 6.25-6.52, disrupting protein glycosylation maturation, particularly O-glycosylation and sialylation 1. ATP6V0A2 also regulates endosomal pH-sensing machinery and supports autophagy through proper vesicular acidification 2. Pathogenic variants in ATP6V0A2 cause autosomal recessive cutis laxa type 2A (ARCL2A), characterized by wrinkled, sagging skin, facial dysmorphisms, delayed anterior fontanelle closure, and developmental delays 34. Additionally, ATP6V0A2 mutations cause wrinkly skin syndrome (WSS), with glycosylation defects, impaired cortical neuron migration, and previously unrecognized male infertility due to globozoospermia and defective acrosome formation 1. Senescence-associated downregulation of ATP6V0A2 triggers Golgi dispersion and altered glycosylation patterns characteristic of cellular aging 5. ATP6V0A2 dysfunction represents a metabolic form of cutis laxa involving aberrant protein glycosylation and trafficking 6.