In an ischemia-reperfusion injury model, exercise preconditioning relies on the Musclin-cyclic guanosine monophosphate (cGMP)/PKGI/CREB/PGC1α signaling axis to activate mitochondrial biogenesis,71 and knocking out Musclin completely abolishes the cardioprotective effects of exercise.70 Here, OSTN is linked to ischemia reperfusion injury.