3-hydroxyacyl-CoA dehydrogenase type-2

HSD17B10 (3-hydroxyacyl-CoA dehydrogenase type-2) is a mitochondrial enzyme with multiple metabolic functions, including catalysis of the third step in fatty acid beta-oxidation and involvement in branched-chain amino acid and steroid metabolism (UniProt: Q99714). The protein also exhibits hydroxysteroid dehydrogenase activity toward steroid hormones and bile acids, notably oxidizing allopregnanolone—a modulator of GABAergic signaling. Additionally, HSD17B10 moonlights as a component of mitochondrial ribonuclease P and participates in tRNA maturation and mitochondrial nucleoid organization.

Mutations in HSD17B10 cause HSD10 mitochondrial disease (HSD10MD; MIM 300438), an X-linked disorder characterized by progressive neurodegeneration, psychomotor retardation, seizures, and cardiomyopathy (UniProt: Q99714). The protein is essential for mitochondrial structural and functional integrity across tissues, with particular relevance to neuronal function.

HSD17B10 is curated as Alzheimer's Disease-relevant and is upregulated in post-mortem AD brain tissue relative to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of 0.58 across analyzed fractions. UniProt notes that HSD17B10 may contribute to neuronal dysfunction in AD through direct interaction with intracellular amyloid-beta, suggesting a mechanistic link to disease pathology.