ATP6V1E1 encodes the E1 subunit of the V1 domain of vacuolar H+-ATPase (V-ATPase), a multisubunit enzyme complex responsible for ATP hydrolysis and proton translocation 1. The V-ATPase complex acidifies intracellular compartments including lysosomes, endosomes, and secretory granules, and in some cell types localizes to the plasma membrane for extracellular acidification 1. ATP6V1E1 mutations cause autosomal-recessive cutis laxa with dysmorphic features and cardiopulmonary involvement; these mutations impair V-ATPase assembly and stability, disrupting protein glycosylation and vesicular trafficking while causing abnormal elastic and collagen fiber organization 2. ATP6V1E1 is classified as a congenital disorder of glycosylation (CDG) gene 34. Beyond cutis laxa, ATP6V1E1 dysfunction has been implicated in Alzheimer's disease pathogenesis, where downregulation correlates with amyloid-beta and tau pathology and impairs lysosomal acidification 567. Additionally, Mycobacterium tuberculosis exploits ATP6V1E1 phosphorylation to suppress lysosomal acidification and promote intracellular survival, suggesting ATP6V1E1 as a therapeutic target for tuberculosis 8.