Traditionally, CyPD has been thought to regulate the opening of the permeability transition pore (PTP), a large conductance pore whose opening depolarizes the inner mitochondrial membrane (IMM) to decrease ATP and increase reactive oxygen species production, and drugs that inhibit CyPD have been used in animal and human studies to protect tissues against various insults, such as ischemia–reperfusion injury (IRI). Here, PPIF is linked to ischemia reperfusion injury.