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.