Myocardial ischemia-reperfusion (MI/R) injury is a leading cause of morbidity and mortality around the world, characterized by injury to cardiomyocytes that leads to various forms of cell death, including necrosis, apoptosis, autophagy, and ferroptosis. Preventing cell death is crucial for preserving cardiac function after ischemia-reperfusion injury. Ferroptosis, a novel type of cell death, has recently been identified as a key driver of cardiomyocyte death following MI/R. However, the complex regulatory mechanisms involved in ferroptosis remain unclear. Here, we found that SENP2 expression decreased following myocardial ischemia reperfusion injury. Deletion of