We found that pharmacological inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP), a selective inhibitor of EZH2, or siRNA-mediated silencing of EZH2, protects against AKI and alleviates renal tubular cell death in the murine kidney of I/R or FA-induced AKI. The gene discussed is EZH2; the disease is acute kidney injury.