Mechanistically, SIRT5 desuccinylated PRDX6 at lysine 209, thereby inhibiting inflammatory and oxidative stress responses, attenuating ferroptosis, and ultimately ameliorating renal injury.<h4>Conclusion</h4>The SIRT5-PRDX6 axis regulates SA-AKI pathogenesis by modulating ferroptosis and represents a novel potential therapeutic target. The gene discussed is SIRT5; the disease is acute kidney injury.