ACSL4 and ischemic stroke: As discussed above, thrombin partners with cPLA2α to release AA from the membrane,44 and ACSL4 catalyzes the esterification of AA into PE.36 AA-PE is the primary substrate for iron-induced peroxidation in ferroptosis.68 The loss of ACSL4 during ischemic stroke as we reported here (Fig. 6b), therefore, may be a neuroprotective response that we show can be amplified if ACSL4 is suppressed or inhibited (Fig. 7f–h, m, n and Supplementary Fig. S4c–f).