SNCA and Parkinson disease: Applying the system to human-induced pluripotent stem cell (hiPSC)-derived dopaminergic neurons from a Parkinson’s disease patient with the SNCA triplication resulted in robust and steady downregulation of SNCA mRNA and protein levels, mediated by targeted DNA methylation at a regulatory sequence located in intron 1 of SNCA. We further demonstrated that this reduction in SNCA levels is capable of rescuing disease-related phenotypes.