HSD17B8 (hydroxysteroid 17-beta dehydrogenase 8) is a multifunctional enzyme with dual roles in steroid metabolism and mitochondrial fatty acid biosynthesis. As part of mitochondrial fatty acid synthesis (mtFAS), HSD17B8 serves as the α-subunit of the heterotetramer 3-ketoacyl-ACP reductase (KAR) complex, acting as a scaffold protein essential for the stability and function of the β-subunit CBR4 1. This complex utilizes NADPH and ACP to reduce 3-ketoacyl-ACP intermediates in mitochondrial fatty acid biosynthesis 1. HSD17B8 also exhibits NAD-dependent 3R-hydroxyacyl-CoA dehydrogenase activity, potentially routing metabolic intermediates into mitochondrial β-oxidation pathways 1 2. In steroid metabolism, HSD17B8 functions as an NAD-dependent 17β-hydroxysteroid dehydrogenase with highest activity toward estradiol, primarily catalyzing the oxidation of estradiol to estrone 3. The enzyme is transcriptionally regulated by estrogen receptor α (ERα) through interaction with C/EBPβ, creating a feedback mechanism in estrogen metabolism 3. Clinically, HSD17B8 expression is associated with better prognosis in breast cancer patients 4 and serves as a biomarker for thyroid cancer dedifferentiation 5. Additionally, altered HSD17B8 levels have been implicated in idiopathic pulmonary fibrosis pathogenesis 6.