Human Aldo-Keto Reductase Family 1 Member C4 (AKR1C4) Protein

Background

AKR1C4 is primarily expressed in the liver and functions as a key enzyme in bile acid biosynthesis and steroid metabolism. It catalyzes the reduction of ketosteroids, including androgens, estrogens, and progestins, to their inactive metabolites, maintaining steroid hormone balance. AKR1C4 is highly active in converting 5α-dihydrotestosterone (DHT) and progesterone to their respective inactive 3α-hydroxy derivatives, thus playing a protective role in preventing excessive androgen and progesterone signaling. Its liver-specific expression makes it central to hepatic detoxification, where it metabolizes reactive carbonyl species and exogenous toxins, protecting hepatocytes from oxidative stress. Dysregulation of AKR1C4 has been associated with liver diseases, including hepatocellular carcinoma, where it contributes to metabolic reprogramming and tumor progression. AKR1C4 also influences bile acid synthesis and lipid metabolism, highlighting its role in maintaining liver homeostasis. Its involvement in steroid and detoxification pathways makes it a potential target for liver diseases and hormone-related disorders.