Role of HSD17B13 in the liver physiology and pathophysiology

17β-Hydroxysteroid dehydrogenases (HSD17Bs) comprise a large family of 15 members that are mainly involved in sex hormone metabolism. Some HSD17Bs enzymes also play key roles in cholesterol and fatty acid metabolism. Recent study showed that hydroxysteroid 17β-dehydrogenase 13 (HSD17B13), an enzyme with unknown biological function, is a novel liver-specific lipid droplet (LD)-associated protein in mouse and humans. HSD17B13 expression is markedly upregulated in patients and mice with non-alcoholic fatty liver disease (NAFLD). Hepatic overexpression of HSD17B13 promotes lipid accumulation in the liver. In this review, we summarize recent progress regarding the role of HSD17B13 in the regulation of hepatic lipid homeostasis and discuss genetic, genomic and proteomic evidence supporting the pathogenic role of HSD17B13 in NAFLD. We also emphasize its potential as a biomarker of advanced liver disease, such as non-alcoholic steatohepatitis (NASH) and liver cancer. •NAFLD is characterized by a massive accumulation of lipid droplets.•HSD17B13 is a newly identified liver restricted LD-associated protein.•HSD17B13 expression is markedly upregulated in the livers of patients and mice with NAFLD.•A variant in HSD17B13 (rs72613567:TA) is negatively associated with ALT and AST levels.•The physiological function of HSD17B13 remains largely uncharacterized.