17β-hydroxysteroid dehydrogenase 13 (HSD17B13)

17β-Hydroxysteroid dehydrogenase 13 (HSD17B13) is a liver-specific enzyme encoded by the HSD17B13 gene on chromosome 4q22.1, primarily localized to lipid droplets in hepatocytes where it plays a key role in hepatic lipid metabolism. It exhibits retinol dehydrogenase activity and oxidizes various lipid substrates including 17β-estradiol, retinal, leukotriene B4, and fatty acids, contributing to lipogenesis and lipid homeostasis. Expression is markedly upregulated in nonalcoholic fatty liver disease (NAFLD), promoting steatosis, though certain loss-of-function variants (e.g., rs72613567 splice variant, rs62305723 P260S mutation) protect against progression to inflammation, ballooning, fibrosis, and hepatocellular carcinoma. HSD17B13 forms homodimers and requires N-terminal sequences (e.g., AA22-28, AA71-106) for lipid droplet targeting and proper folding/trafficking from the endoplasmic reticulum. As an emerging therapeutic target for metabolic liver diseases like NAFLD/NASH, inhibitors binding the active site and NAD+ cofactor are under development to mimic protective variants and halt disease progression.

Other names

17-beta-hydroxysteroid dehydrogenase 13hydroxysteroid 17-beta dehydrogenase 13short-chain dehydrogenase/reductase family 16C member 3SDR16C3short-chain dehydrogenase/reductase 9SCDR917-beta-HSD 13hepatic retinol/retinal dehydrogenase

Inhibition of enzymatic activity (retinol oxidation, lipid substrate oxidation) to reduce hepatic lipid accumulation and protect against steatosis progression