DHRS6 (dehydrogenase/reductase SDR family member 6), also known as EFA6R, SDR15C1, UCPA-OR,UNQ6308 or BDH2, is a 245 amino acid cytoplasmic protein belonging to the short-chain dehydrogenases/reductases (SDR) family, an evolutionarily conserved family of oxidoreductases found in all forms of life. DHRS6 is a novel, cytosolic type II R-β-hydroxybutyrate dehydrogenase that exists as two alternatively spliced isoforms and may have an essential role as a nutrient or building block in cellular survival. Human DHRS6 and its vertebrate orthologs show high levels of sequence identities to bacterial hydroxybutyrate dehydrogenases. DHRS6 may play an important role in the peripheral utilization of 3-hydroxybutyrate and its cytoplasmic localization with its high ratio of oxidized NAD+, the NAD+ dependence and the kinetic parameters of DHRS6 make it suitable to convert high levels of circulating 3-hydroxybutyrate into acetoacetate.