17β-Hydroxysteroid dehydrogenase type 4 (17β-HSD4)

17β-Hydroxysteroid dehydrogenase type 4 (17β-HSD4, also known as D-bifunctional protein or peroxisomal multifunctional enzyme type 2) is a bifunctional oxidoreductase enzyme encoded by the HSD17B4 gene in humans. It is predominantly localized in peroxisomes, where it catalyzes two critical steps of fatty acid β-oxidation, essential for the degradation of very-long-chain and branched-chain fatty acids. In steroid metabolism, it mediates the oxidative conversion of 17β-hydroxysteroids (such as estradiol to estrone), thus regulating the availability of active androgens and estrogens in peripheral tissues. Mutations in the gene lead to D-bifunctional protein deficiency and are implicated in metabolic and developmental disorders. Aberrant expression has been associated with cancer cell metabolism and tumor progression, highlighting its relevance as a potential therapeutic target, particularly in hormone-responsive cancers.

Other names

D-bifunctional protein (DBP)Peroxisomal multifunctional enzyme type 2 (MFP-2)17β-Hydroxysteroid dehydrogenase type IVSDR8C1

Inhibition of HSD17B4 could block both fatty acid β-oxidation in peroxisomes and the metabolism of steroid hormones (estradiol to estrone; androgen/estrogen catabolism), potentially altering hormone levels in tissues and affecting tumor growth/metabolism