We showed that both structural and functional renal deterioration in CKD mice was markedly reversed by FGF1ΔHBS-mediated AKT activation associated with the inhibition of apoptosis signal-regulating kinase 1 (ASK1)-mediated c-Jun N-terminal kinase (JNK) activation and the restoration of cellular redox homeostasis via the GSK-3β/Nuclear factor erythroid-2-related factor 2 (Nrf2) signaling cascade. Here, MAP3K5 is linked to chronic kidney disease.