• ABL1 expression is significantly downregulated in cardiac ischemia/reperfusion injury and oxidative stress models.
• Knockdown of ABL1 exacerbates cardiac dysfunction, myocardial fibrosis, and ventricular remodeling after ischemia/reperfusion.
• ABL1 knockdown increases oxidative stress-induced cell death, necroptosis, and reactive oxygen species accumulation in cardiomyocytes.
• ABL1 exerts cardioprotective effects by targeting the Parkin-CypD pathway to regulate mitochondrial membrane permeability.