17-beta-hydroxysteroid dehydrogenase type 10 (17β-HSD10 (also HSD10))

17-beta-hydroxysteroid dehydrogenase type 10 is a multifunctional mitochondrial enzyme encoded by the HSD17B10 gene on chromosome Xp11.22. It belongs to the short-chain dehydrogenase/reductase superfamily and forms homotetramers within mitochondria. The enzyme catalyzes key steps in the oxidation of various substrates including neuroactive steroids, branched-chain fatty acids, bile acids, xenobiotics, and particularly plays a critical role in isoleucine catabolism. Beyond metabolic functions—such as converting potent estrogens into weaker forms and generating dihydrotestosterone from precursors—it also participates in tRNA maturation via its role as a subunit of mitochondrial ribonuclease P complex. Mutations cause severe neurological disorders ranging from infantile neurodegeneration with psychomotor regression to X-linked intellectual disability syndromes. Abnormalities have been linked with Alzheimer's disease through direct binding with amyloid-beta peptide leading to mitochondrial dysfunction; overexpression has also been observed in some cancers such as prostate cancer. Due to these diverse roles—in neuronal health/disease mechanisms—and interactions with key signaling molecules like amyloid-beta peptide and steroid hormones—this enzyme represents an emerging therapeutic target for both neurological diseases like Alzheimer's disease and certain malignancies.

Other names

Hydroxysteroid 17-beta dehydrogenase 10HSD17B10SDR5C1MRPP2ERAB (Endoplasmic Reticulum-Associated Amyloid Beta-Peptide-Binding Protein)MHBD (2-methyl-3-hydroxybutyryl-CoA dehydrogenase)HADH2ABAD (Aβ-binding alcohol dehydrogenase)CAMRMitochondrial ribonuclease P protein 2Mitochondrial RNase P subunit 2

Drugs or compounds targeting this enzyme would likely act by inhibiting or modulating its enzymatic activity—affecting steroid hormone levels, neurosteroid metabolism, or mitochondrial function. In Alzheimer’s research, inhibition aims to disrupt the interaction between HSD10/ABAD and amyloid-beta peptide to reduce mitochondrial dysfunction.