Endosomal/lysosomal proton channel TMEM175

Proton-activated proton channel that catalyzes proton efflux from endosomes and lysosomes to maintain a steady-state pH. Activated at low pH (under pH 4.6) by luminal side protons: selectively mediates lysosomal proton release from lysosomes, eliciting a proton leak that balances V-ATPase activity to maintain pH homeostasis. Regulation of lumenal pH stability is required for autophagosome-lysosome fusion. May also act as a potassium channel at higher pH, regulating potassium conductance in endosomes and lysosomes. The potassium channel activity is however unclear as it was tested in non-physiological conditions for a lysosomal channel. Constitutes the pore-forming subunit of the lysoK(GF) complex, a complex activated by extracellular growth factors. The lysoK(GF) complex is composed of TMEM175 and AKT (AKT1, AKT2 or AKT3), a major target of growth factor receptors: in the complex, TMEM175 channel is opened by conformational changes by AKT, leading to its activation. The lysoK(GF) complex is required to protect neurons against stress-induced damage.