AKR1D1 (aldo-keto reductase family 1 member D1) is a steroid 5β-reductase predominantly expressed in human liver that serves critical roles in bile acid biosynthesis and steroid hormone metabolism 1. The enzyme catalyzes the stereospecific NADPH-dependent reduction of the C4-C5 double bond in steroid substrates, creating an A/B cis-ring junction essential for bile acid function as emulsifiers 2. AKR1D1 inactivates glucocorticoids and androgens, with overexpression increasing steroid clearance and decreasing glucocorticoid receptor activation, while knockdown has opposite effects 3. The enzyme exists as multiple splice variants, with AKR1D1-002 being the predominant functional form in liver 4. AKR1D1 expression is significantly decreased in non-alcoholic fatty liver disease (NAFLD), correlating with advancing steatosis and fibrosis 5. Knockdown of AKR1D1 promotes hepatocyte lipid accumulation and inflammation through disrupted bile acid synthesis 5. Recent studies reveal AKR1D1's role in liver cancer suppression by regulating bile acid metabolism and NK cell cytotoxicity 6. Mutations in AKR1D1 cause congenital bile acid synthesis defect 2, leading to cholestasis and potential liver damage 1. Certain anabolic steroids can inhibit AKR1D1 activity, potentially contributing to steroid-induced hepatotoxicity 7.