Abstract: Apoptosis signal-regulating kinase 1（ASK1）, a member of the mitogen-activated protein kinase kinase kinase（MAP3K） family, can respond to a variety of stress stimuli, such as oxidative stress and endoplasmic reticulum（ER） stress, thereby activating the c-Jun N-terminal kinase（JNK） and p38 mitogen-activated protein kinase（p38 MAPK） signaling pathways in downstream mitogen-activated protein kinase（MAPK） to regulate apoptosis, inflammation, and fibrosis, mediating acute kidney injury（AKI）, diabetic kidney disease（DKD）, cardiorenal syndrome（CRS） and other renal diseases. In this review, we discuss the major activation and inactivation mechanisms of ASK1, its role in the progression of multiple renal diseases. We also provide an overview of GS-4997, GS444217 and GS459679, the inhibitors of ASK1, to explore the potential of ASK1 inhibitors in clinical applications.