ATP13A2 (PARK9), a P5-type ATPase, is associated with autosomal recessive early-onset Parkinson's disease (PD), known as Kufor-Rakeb syndrome. In the present study, we found that ATP13A2 functions as a novel lysosomal H⁺,K⁺-ATPase that transports K⁺ from the lysosomal lumen to the cytoplasm and H⁺ from the cytoplasm to the lysosomal lumen. Interestingly, ATP13A2 has unique pharmacological properties: its K⁺-ATPase activity was significantly inhibited by K⁺-competitive acid blockers (P-CABs) vonoprazan (IC₅₀ = 0.8 μM) and SCH28080 (IC₅₀ = 1.2 μM), and a vacuolar H⁺-ATPase inhibitor bafilomycin A1 (IC₅₀ = 0.5 nM). On the other hand, a proton pump inhibitor (PPI) omeprazole and a Na⁺,K⁺-ATPase inhibitor ouabain did not affect the ATPase activity. The inhibition of ATP13A2 activity by P-CABs caused lysosomal alkalinization and α-synuclein accumulation, which are pathological hallmarks of PD, in human neuronal SH-SY5Y cells. In addition, PD-associated mutations of ATP13A2 markedly reduced the expression and K⁺-transporting activity of the ATPase. These results suggest that the H⁺/K⁺-transporting function of ATP13A2 contributes to acidification and α-synuclein degradation in the lysosomes of neurons.