The most common LRRK2 mutation associated with PD, G2019S, is located in the kinase domain and causes a modest 2-fold increase in kinase activity and phosphorylation of substrates in vitro [77] and in vivo [97], while increasing the LRRK2G2019S autophosphorylation activity 4-fold [98]. Here, LRRK2 is linked to Parkinson disease.