ATP6V1D is a subunit of the vacuolar H+-ATPase (V-ATPase) V1 complex, which catalyzes ATP hydrolysis to drive proton translocation across membranes 1. As part of the V-ATPase holoenzyme, ATP6V1D functions in acidifying intracellular compartments including lysosomes and endosomes, and may regulate cilium biogenesis through protein transport and localization 2. ATP6V1D plays critical roles in lysosomal homeostasis by maintaining autophagic flux through lysosomal acidification and ESCRT-III complex assembly 3. Assembly of ATP6V1D into the V1 subcomplex is regulated by ABL1-mediated phosphorylation of ATP6V1B2, which facilitates V-ATPase integration and autophagy-dependent mitochondrial clearance 4. ATP6V1D interacts with ATG16L1 following its deacetylation, enabling LC3-associated microautophagy and lysosomal recovery under stress conditions 5. Clinically, ATP6V1D downregulation correlates with reduced Alzheimer's disease risk as a protective factor, potentially through regulation of inflammatory pathways 6. In hepatocellular carcinoma, elevated ATP6V1D expression promotes cancer stem cell properties and poor clinical outcomes, making it a therapeutic target 3. Decreased urinary ATP6V1D levels serve as a diagnostic biomarker for IgA nephropathy discrimination 7, while reduced expression in renal clear cell carcinoma associates with favorable prognosis 8.