In the study, we presented the following findings: (a) FABP4 was markedly upregulated in RTECs in experimental models of septic AKI; (b) functionally, inhibition of FABP4 attenuated sepsis-induced kidney injury, and particularly, RTEC-specific deletion of FABP4 also showed similar renoprotective effects; (c) mechanistically, upregulation of tubular FABP4 in septic AKI was mediated by TLR4/c-Jun signaling activation, and FABP4 formed a positive feedback loop with c-Jun to exacerbate kidney inflammation and apoptosis. Here, JUN is linked to acute kidney injury.