Acute kidney injury(AKI)is characterized by high morbidity,high mortality,high disability rate and high treatment cost,its pathological mechanism has not been fully elucidated and there is a lack of ef-fective treatment methods.Klotho,a kidney-specific protective protein,is mainly expressed in renal tubular ep-ithelial cells,regulates the AKI progression and mitigates the renal injury through multiple pathways,inclu-ding the regulation of the renin-angiotensin-aldosterone system(RAAS),antioxidant stress,anti-inflamma-tion,modulation of cell death and anti-fibrotic effects.At present,the Klotho-based strategies for AKI preven-tion and treatment remain in the preclinical stage,requiring further investigation.This article reviews the mo-lecular regulatory mechanisms of Klotho in AKI and its diagnostic and therapeutic potential,aiming to provide new idea for the pathological mechanisms and clinical translation of AKI.