Our data demonstrated that Roc-A induces mitophagy by the PINK1/Parkin signal pathway and provokes PC cell apoptosis by generation of intracellular ROS, loss of the Δψm, and release of cytochrome c. We also found that inhibition of autophagy/mitophagy can augment Roc-A-induced cell apoptosis in PC cells. Here, CYCS is linked to pachyonychia congenita.