Previous studies have established that LRRK2 lies within an endo-lysosomal signaling network with other PD gene-encoded proteins including VPS35, RAB29, and RAB32 that act upstream of LRRK2 and in which disease-associated mutations lead to LRRK2 hyperactivation and increased Rab phosphorylation (14, 46, 59, 60). This evidence concerns the gene VPS35 and Parkinson disease.