Dai et al. identified that ACSL4 in kidney fibrosis increase ferroptotic precursors of tubular epithelial cells by modulating arachidonic acid (AA) and adrenic acid (AdA) of polyunsaturated fatty acids (PUFA). Inhibition of ferroptosis by targeting ACSL4 rescued tubular epithelial cells ferroptosis and alleviated kidney fibrosis, which provide more potential therapeutic approaches.