Here, ERK has been etiologically implicated in brain injury following cerebral ischemia/reperfusion owing to its ability to inhibit MPTP by downregulating CypD expression, and the resistance displayed by GA were abrogated by co-administration of U0126 in vitro and in vivo, further confirming that the neuroprotective effect of GA is depending on regulating the ERK-CypD axis. Here, PPIF is linked to Cerebral ischemia.