While no large-scale trials have yet tested EPHX2 inhibitors in CKD patients, preclinical models provide compelling support: genetic deletion or pharmacological blockade of sEH attenuates renal inflammation and tubulointerstitial fibrosis in multiple CKD models (e.g., diabetic nephropathy, remnant kidney, high-fat diet) through enhanced EET bioavailability and modulation of oxidative stress and autophagy pathways [72,194]. Here, EPHX2 is linked to diabetic kidney disease.