Using both in vivo AKI murine models and in vitro cisplatin-exposed mouse proximal tubule cells (TKPTS) lines, combined with metabolomics analysis, we further demonstrated that maintaining renal Slc25a21 expression protects renal tubules from cisplatin-induced damage and alleviates cell apoptosis and necroptosis as well as inflammation, thereby preventing the progression of AKI. The gene discussed is SLC25A21; the disease is acute kidney injury.