TLDC2 is a TLDc domain-containing protein that functions as a negative regulator of vacuolar-type ATPase (V-ATPase). Its primary role is to inhibit V-ATPase activity by inducing disassembly of the V-ATPase complex 1. TLDC2 belongs to an evolutionarily conserved family of V-ATPase regulatory proteins, with the TLDc domain being essential for this interaction 2. Beyond V-ATPase regulation, TLDC2 is implicated in protecting neuronal cells against oxidative stress and is required for kidney bicarbonate secretion 1. The protein localizes to the nucleus and responds to oxidative stress conditions. Functionally, TLDC2 represents a distinct class of V-ATPase-interacting regulatory proteins that fine-tune proton pump function through controlled enzyme disassembly rather than simple inhibition. Additionally, TLDC2 has been identified as a hub gene in co-expression networks associated with cutaneous leishmaniasis immune response, suggesting potential roles in host-pathogen interactions and immune signaling 3. The clinical significance of TLDC2 dysfunction may relate to neurological disease phenotypes that mirror V-ATPase deficiency, though direct human disease associations require further investigation.