CDK5 and Parkinson disease: In the current study, we indicated that a mechanism of gene-environment interaction and “two-hot” model were involved in the progress of PD patients with genetic R1628P mutation, that the R1628P mutation do not alter the LRRK2 kinase activity and cause neuronal death per se, but rather increases the susceptibility of carriers to environment toxins or aging stress, which consequently activated Cdk5[10, 11].