Hsdl2, or hydroxysteroid dehydrogenase-like 2, is a protein-coding gene. It plays a crucial role in lipid metabolism, linking nutritional cues to bile acid and cholesterol homeostasis [1]. It is also involved in regulating cell proliferation, and is associated with various metabolic and cancer-related pathways. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying its functions.

In KO-related studies, Hsdl2 depletion in hepatocytes decreases cholesterol conversion to bile acids, impairs FXR activity, reduces mitochondrial respiration, fatty acid oxidation, and TCA cycle activity, affecting BA metabolism and circulating cholesterol levels upon refeeding [1]. In cancer research, knockdown of Hsdl2 in bladder cancer cells inhibits proliferation and colony formation while promoting apoptosis in vitro and tumor growth inhibition in vivo [2]. In cholangiocarcinoma, Hsdl2 knockdown promotes cancer progression by inhibiting ferroptosis through the P53/SLC7A11 axis [3]. In rectal cancer, Hsdl2 overexpression promotes cell proliferation and cell cycle progression [4]. In pancreatic cancer, silencing Hsdl2 reduces cell proliferation and inhibits lipid metabolism [5]. In lung adenocarcinoma, Hsdl2 knockdown inhibits cell proliferation, invasion, and migration in vitro and tumor growth and metastasis in vivo, and is related to the regulation of AKT2 expression [6]. In papillary thyroid carcinoma, inhibiting Hsdl2 expression suppresses cell proliferation and promotes apoptosis in vitro and in vivo [7].

In conclusion, Hsdl2 is essential in lipid metabolism and cell proliferation regulation. Model-based research, especially KO/CKO mouse models, has significantly contributed to understanding its role in metabolic disorders and various cancers, providing potential therapeutic targets for these disease areas.