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.