Lysosome pH-regulated H + /K + switching channel involved in maintaining lysosomal homeostasis.

Lysosomal pH setpoint and H + homeostasis is key to the lysosome's functions. The Parkinson's disease-risk protein TMEM175, originally identified as lysosomal K + channel, works as a H + -activated H + channel and discharges the lysosomal H + store when it is hyper-acidified. Yang et al. indicate that TMEM175 is permeable for both K + and H + in the same pore and charges the lysosome with H + under certain conditions. The charge and discharge functions are under regulation of the lysosomal matrix and glycocalyx layer. Their presented work indicates that TMEM175 performs as a multi-functional channel regulating lysosomal pH in response to physiological conditions.