Objective Impaired lysosomal degradation of alpha-synuclein and other cellular constituents may play an important role in Parkinson's disease (PD). Rare genetic variants in the glucocerebrosidase (GBA) gene were consistently associated with PD. Here we examine the association between rare variants in lysosomal candidate genes and PD. Methods We investigated the association between PD and rare genetic variants in 23 lysosomal candidate genes in 4096 patients with PD and an equal number of controls using pooled targeted next-generation DNA sequencing. Genewise association of rare variants in cases or controls was analyzed using the optimized sequence kernel association test with Bonferroni correction for the 23 tested genes. Results We confirm the association of rare variants inGBAwith PD and report novel associations for rare variants inATP13A2,LAMP1,TMEM175, andVPS13C. Conclusion Rare variants in selected lysosomal genes, first and foremostGBA, are associated with PD. Rare variants inATP13A2andVPC13Cpreviously linked to monogenic PD and more common variants inTMEM175andVPS13Cpreviously linked to sporadic PD in genome-wide association studies are associated with PD.