Hydroxysteroid dehydrogenase-like protein 2 (HSDL2)

Hydroxysteroid dehydrogenase-like protein 2 (HSDL2) is an evolutionarily conserved enzyme belonging to the short-chain dehydrogenase/reductase (SDR) family, characterized by an N-terminal SDR domain and a C-terminal sterol carrier protein 2 (SCP2) domain[1][2][4]. It is primarily localized to mitochondria and peroxisomes, where it regulates lipid metabolic processes, including fatty acid synthesis, β-oxidation, and cholesterol homeostasis[1][2]. HSDL2 is involved in the conversion of cholesterol to bile acids and influences activation of the nuclear bile acid receptor FXR, linking nutritional cues (e.g., fasting/feeding) to metabolic responses[2]. Overexpression or dysregulation of HSDL2 has been implicated in enhanced proliferation, migration, and survival in several cancers, such as papillary thyroid carcinoma and glioma, highlighting its dual role as both a metabolic regulator and a potential oncogene in tumorigenesis[1][3][4]. Its expression and functional impact are context-dependent across tissues, and it is under investigation as both a prognostic biomarker and a therapeutic target[1][3]. Currently, no specific drugs are listed as direct HSDL2 inhibitors or modulators, and its full clinical therapeutic profile remains under investigation.

Other names

HSDL2C9orf99SDR13C1Short chain dehydrogenase/reductase family 13C member 1Hydroxysteroid dehydrogenase-like 2Short chain dehydrogenase/reductase family 13C, member 1

Modulation of lipid and cholesterol metabolism Regulation of cholesterol conversion to bile acids Influence on FXR (Farnesoid X receptor) activation and associated signaling pathways Potential modulation of AKT-associated signaling (in cancer)