Herein, we demonstrated that depletion of Prx5 exacerbated the loss of Δψm and increased cytochrome c release, followed by activation of the caspase-9- and caspase-3-dependent intrinsic apoptotic pathway after rotenone treatment, suggesting that Prx5 had anti-apoptotic effects in this cellular model of PD. Here, CASP9 is linked to Parkinson disease.