During this phase, Caspase 3 can cleave GSDME, triggering secondary pyroptosis.42,46,47 In our study, the overexpression of p21 can activate the Caspase 3 and GSDME, finally resulting in mitochondrial dysfunction, apoptosis and Caspase 3/GSDME‐dependent secondary pyroptosis in PTECs and aggravated cisplatin induced AKI. The gene discussed is CDKN1A; the disease is acute kidney injury.