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.