The HSD17B10 gene maps on chromosome Xp11.2, a region highly associated with X-linked mental retardation. This gene encodes HSD10, a mitochondrial multifunctional enzyme that plays a significant part in the metabolism of neuroactive steroids and the degradation of isoleucine. The HSD17B10 gene is composed of six exons and five introns. Its exon 5 is an alternative exon such that there are several HSD17B10 mRNA isoforms in brain. A silent mutation (c.605C-->A) and three missense mutations (c.395C-->G; c.419C-->T; c.771A-->G), respectively, cause the X-linked mental retardation, choreoathetosis, and abnormal behavior (MRXS10) and the hydroxyacyl-CoA dehydrogenase II deficiency. The latter condition seems to be a multifactorial disease due to the disturbance of more than one metabolic pathway by the HSD10 deficiency. HSD10 inactivates the positive modulators of GABAA receptors, and plays a role in the maintenance of GABAergic neuronal function. This working model may account for the mental retardation of these patients. The dehydrogenase activity is slightly inhibited by the binding of amyloid-beta peptide to the loop D of HSD10. Elevated levels of HSD10 were observed in hippocampi of Alzheimer disease patients so this multifunctional enzyme may be related to Alzheimer disease pathogenesis; however, the molecular mechanism of its involvement remains to be ascertained.