Leucine-rich repeat kinase 2 (LRRK2), encoded by LRRK2 gene, is a large (286 kDa), multi-domain protein that, in addition to its kinase domain, possesses a second enzymatic guanosine triphosphatase (GTPase) domain and several other domains and motifs that are involved in protein-protein interactions . Pathological mutations in the kinase domain and GTPase domain of LRRK2, such as G2019S and R1441C/G/H mutations, can increase the kinase activity of LRRK2 and eventually lead to pathogenic hallmarks associated with PD, such as ciliogenesis inhibition , defective mitophagy and autophagy , and mitochondrial dysfunction . Increased LRRK2 kinase activity, independent of LRRK2 mutations, has also been reported in idiopathic PD patients . Conversely, LRRK2 knockout or pharmacological inhibition of LRRK2 kinase activity are neuroprotective in cellular and in animal models . These observations provide strong rationale for targeting LRRK2 to treat PD.