Atp6v1d, also known as ATPase H+ transporting V1 subunit D, is a subunit of the vacuolar-type H+-translocating ATPase (V-ATPase). V-ATPase is involved in processes such as lysosomal acidification and autophagy-lysosomal pathway, which are crucial for maintaining cellular homeostasis and normal biological functions [1,2,3,6].

In hepatocellular carcinoma (HCC), ATP6V1D knockdown inhibits HCC stemness and malignant progression both in vitro and in vivo. Mechanistically, it enhances HCC stemness and progression by maintaining autophagic flux, through promoting lysosomal acidification and enhancing the interaction between CHMP4B and IST1 to foster ESCRT-III complex assembly, thus facilitating autophagosome-lysosome fusion [1].

In Alzheimer's disease, ATP6V1D has been identified as a biomarker, and its down-regulated expression is considered a protective factor. It is potentially involved in pathways related to "interferon gamma response", "inflammatory response", and "TNFα signaling via NFκB" [4].

In depression, SNPs (rs3759755 and rs10144417) in the promoter region of the ATP6V1D are associated with susceptibility to depression [5].

In conclusion, Atp6v1d plays a significant role in multiple biological processes mainly through its involvement in the autophagy-lysosomal pathway. Its functions are closely related to diseases like HCC, Alzheimer's disease, and depression. Studies on Atp6v1d knockout or knockdown models have provided valuable insights into the underlying mechanisms of these diseases, helping to understand the biological functions of Atp6v1d and offering potential therapeutic targets for related diseases [1,4,5].