Ferroportin (FPN) knockout (KO) by Nestin-Cre increased FTH1 and glutathione peroxidase-4 (GPx4) and decreased NADPH oxidase-4 (NOX4) and apoptosis in ischemia/reperfusion (I/R) kidneys. Western blot (A) and densitometric analysis (B) showed increased ferritin (FTH1) in both sham and I/R floxed FPN (FPNf/f)/Nestin-Cre vs. WT kidneys. C and D: NOX4 and heme oxygenase-1 (HO-1) proteins were decreased and GPx4 was increased in I/R kidneys of FPNf/f/Nestin-Cre vs. WT mice, and GPx1, GPx6, and catalase were comparable, respectively. E and F: phosphorylated receptor-interacting Ser/Thr kinase-3 (p-RIPK3) was comparable, and Bax and cleaved caspase-3 were decreased in I/R kidneys of FPNf/f/Nestin-Cre vs. WT mice. Data are presented as means ± SE (3 mo; n = 3, male) and were analyzed using two-way ANOVA followed by post hoc Tukey’s HSD test.