In summary, the PD-associated pathogenic LRRK2 mutations increase phosphorylation of LRRK2 kinase substrates in vivo [31] and are associated with: (1) alterations in the regulation of macroautophagy under different cellular conditions, (2) impaired lysosomal function with abnormal lysosomal morphology and increased alkalinization, (3) altered endolysosomal trafficking mediated by increased phosphorylation of a subset of Rab GTPases, and (4) impaired CMA by enhanced binding to LAMP2A and blockage of degradation of other CMA substrates including α-syn. The gene discussed is LRRK2; the disease is Parkinson disease.