ATP6AP2 is a multifunctional X-linked gene encoding a protein with dual roles in cellular homeostasis. Functionally, ATP6AP2 serves as a (pro)renin receptor and as an accessory subunit of the V-type ATPase (V-ATPase) complex 1. Through its V-ATPase function, ATP6AP2 mediates lysosomal acidification and endo-lysosomal system function, critical for protein degradation and autophagy 2. As a renin receptor, ATP6AP2 participates in local renin-angiotensin system signaling within tissues including the brain, pancreas, and cardiovascular system 134. Clinically, ATP6AP2 mutations cause X-linked neurological disorders. Splicing variants cause X-linked intellectual disability (Hedera type) and X-linked parkinsonism with spasticity, characterized by developmental delay, epilepsy, and abnormal glycosylation 56. Missense mutations lead to congenital disorder of glycosylation 2R with hepatic involvement 5. ATP6AP2 dysfunction impairs lysosomal biogenesis and cellular viability; restoring lysosomal function can ameliorate defects in affected cells 23. Sex-linked inheritance and X-chromosome X complicate phenotypic presentation, with heterozygous females showing milder manifestations 57. The gene's role in maintaining cellular homeostasis suggests therapeutic potential through targeting lysosomal pathways.