HSDL2 is a mitochondrial protein that functions as a metabolic regulator despite lacking steroid dehydrogenase enzymatic activity 1. Its primary role involves controlling bile acid and lipid metabolism in response to nutritional signals 2. During fasting, HSDL2 expression is induced through PGC1α-PPARα activation and mTORC1 inhibition, promoting cholesterol conversion to bile acids and supporting mitochondrial respiration and fatty acid oxidation 2. HSDL2 depletion impairs FXR activity and reduces TCA cycle function, linking nutritional cues to hepatic homeostasis 2. Beyond metabolic regulation, HSDL2 exhibits oncogenic properties across multiple cancer types. In lung adenocarcinoma and cervical cancer, HSDL2 overexpression promotes proliferation, invasion, and migration through AKT2 signaling and epithelial-mesenchymal transition 34. Conversely, in cholangiocarcinoma, HSDL2 functions as a tumor suppressor; its knockdown promotes progression by inhibiting ferroptosis via the p53/SLC7A11 axis 5. HSDL2 emerges as a potential biomarker in temporal lobe epilepsy, where elevated expression in astrocytes associates with excessive lipid accumulation and seizure-related pathology 6. These diverse roles reflect HSDL2's central involvement in lipid and energy metabolism across physiological and pathological contexts.