LRRK2 and Parkinson disease: Most PD-associated LRRK2 mutations represent gain-of-function alleles: the G2019S and I2020T in the kinase domain cause hyper-phosphorylation of Rabs (West et al., 2005; Gloeckner et al., 2006), and R1441C/G/H in the Roc-COR domain increase kinase activities through disruption of the GTP hydrolysis activity (Weiss, 2008).