Current reports of the pathophysiological mechanism behind LRRK2-PD suggest a toxic gain-of-function mechanism generated from the increased kinase activity caused by variants in the MAPKKK domain (G2019S, I2020T) or indirectly by variants in the COR domain (Y1699C/G) or ROC domain (R1441G/C/H) that reduce the GTPase activity. Here, LRRK2 is linked to Parkinson disease.