PRKN and Parkinson disease: In vitro studies have shown that PINK1 deficiency decreases the viability of human and mouse dopaminergic neuronal cultures.23 In vivo conditional knockdown of PINK1 causes age-dependent loss of dopaminergic neurons in mice.24 Together, this genetic, cell biological, biochemical, and neuropathological evidence establishes PINK1 kinase activity as critical for the survival of dopaminergic neurons in the substantia nigra, the loss of which underlies the motor symptoms of PD and characterizes the primary neuropathology of PD, including PINK1 and Parkin-linked PD.18,21