(A) Pathogenic LRRK2 phosphorylates Rab8 and Rab10 which are normally localized to the pericentriolar early recycling compartment. The phospho-Rab8/10 proteins bind to centrosome-localized RILPL1, which causes centrosomal/ciliary defects. In the axon, pathogenic LRRK2 causes accumulation of phospho-Rab10 on autophagosomes, which is followed by the recruitment of JIP4 and activation of kinesin, thereby interfering with the proper retrograde trafficking of autophagosomes. (B) Lysosomal damage or lysosomal overload, both disease-relevant triggers, cause activation of wildtype LRRK2. Lysosomal damage causes lysosomal accumulation of phospho-Rab10 and JIP4, leading to the vesiculation of lysosomal membranes. Lysosomal overload causes lysosomal accumulation of phospho-Rab10 and EHBP1/EHBP1L1, leading to lysosomal exocytosis.