SERPINE1 (PAI-1), a mediator of inflammation, coagulation dysfunction, and epithelial injury, is frequently elevated in sepsis and ARDS, yet its mechanistic role in ferroptosis remains unknown.<h4>Methods</h4>Transcriptomic analysis of ARDS datasets, LPS-induced mouse models, clinical serum samples, and LPS-stimulated AT2 cells were used to assess SERPINE1 expression. Here, SERPINE1 is linked to acute respiratory distress syndrome.