Using patient samples and a mouse model of sepsis-induced ALI with or without NETs formation inhibited by PAD4 depletion or NETs degradation induced by anti-Ly6G/DNase I treatment, we demonstrate that NETs contribute to the pathology of sepsis-induced ALI by inducing ferroptosis in alveolar epithelial cells. The gene discussed is PADI4; the disease is acute respiratory distress syndrome.