HADH encodes hydroxyacyl-CoA dehydrogenase, a mitochondrial enzyme that catalyzes the third step of fatty acid beta-oxidation for medium and short-chain 3-hydroxy fatty acyl-CoAs (C4 to C10) 1. The enzyme plays a crucial role in fatty acid oxidation (FAO) pathways, which are essential for cellular energy metabolism 1. HADH functions as part of the mitochondrial trifunctional protein complex and participates in steps 2, 3, and 4 of fatty acid beta-oxidation 2. Beyond its metabolic function, HADH has regulatory roles in insulin secretion from pancreatic beta-cells 34. Mutations in HADH cause congenital hyperinsulinism type 4, a rare disorder characterized by inappropriate insulin secretion leading to severe hypoglycemia in neonates and children 563. In clinical studies, HADH mutations account for approximately 16% of diazoxide-responsive hyperinsulinism cases with rare gene mutations 5. The enzyme also plays important roles in cancer metabolism, where abnormal HADH expression affects tumor development and prognosis across multiple cancer types, serving as either a tumor suppressor or promoter depending on tissue context 27. HADH expression is associated with therapeutic response in nasopharyngeal carcinoma and serves as a potential prognostic biomarker 7.