The mechanisms for how neurons die after ischemic stroke are not well understood, and these findings build upon prior results demonstrating the importance of ferroptosis in ischemic disease.16,18 Using proteomics, lipid metabolomics, and immunochemistry, we identified thrombin and its downstream partner in AA metabolism, ACSL4, as critical proteins involved in I/R-related ferroptotic cell death, and thus provide a new understanding of the biochemistry driving ferroptosis in ischemic stroke (Fig. 8). Here, ACSL4 is linked to ischemic stroke.