ATP6V0d2, a subunit of vacuolar ATPase, is highly expressed in macrophages. It plays a crucial role in multiple biological processes. Functionally, it is involved in pathways such as autophagosome-lysosome fusion, and is associated with processes like immune response regulation and cell-cell communication. Genetic models, especially KO mouse models, are valuable for studying its function [2,3,5].

In Atp6v0d2 -/- mice, increased susceptibility to tumor growth was observed. Lactate in the tumor microenvironment suppressed ATP6V0d2 expression via mTORC1 activation, which led to enhanced HIF-2α-mediated VEGF production in macrophages with a more protumoral phenotype [1]. Atp6v0d2-deficient macrophages also showed augmented mitochondrial damage, enhanced inflammasome activation, and reduced clearance of Salmonella typhimurium, highlighting its role in maintaining macrophage organelle homeostasis and limiting inflammation and bacterial infection [2]. In the context of allergic asthma, ATP6V0d2 -/- mice had exaggerated inflammatory cell infiltration and enhanced alternative activated macrophage polarization [4]. Additionally, Atp6v0d2 knockout mice displayed delayed peripheral nerve demyelination and attenuated myelin lipid digestion after nerve injury [5].

In conclusion, ATP6V0d2 is essential for maintaining normal biological functions in macrophages. Through studies using KO mouse models, its significance in tumor progression, immune response to infections, allergic asthma, and peripheral nerve demyelination has been revealed. These findings provide important insights into the underlying mechanisms of these disease conditions and potential therapeutic targets.