Parkinson's disease-associated ATP13A2/PARK9 functions as a lysosomal H,K-ATPase.

Mutations in the human ATP13A2 (PARK9), a lysosomal ATPase, cause Kufor-Rakeb Syndrome, an early-onset form of Parkinson's disease (PD). Here, we demonstrate that ATP13A2 functions as a lysosomal H,K-ATPase. The K-dependent ATPase activity and the lysosomal K-transport activity of ATP13A2 are inhibited by an inhibitor of sarco/endoplasmic reticulum Ca-ATPase, thapsigargin, and K-competitive inhibitors of gastric H,K-ATPase, such as vonoprazan and SCH28080.