• CFAPIR is significantly upregulated in doxorubicin-induced cardiomyopathy and cardiomyocyte ferroptosis models.
• Knockdown of CFAPIR alleviates doxorubicin-induced cardiotoxicity, improving cardiac function and reducing fibrosis.
• CFAPIR knockdown attenuates ferroptosis by modulating iron metabolism, lipid peroxidation, and mitochondrial function.
• CFAPIR may exert its effects by targeting the mitochondrial iron transporter ABCB8.