NADH-cytochrome b5 reductase 3 is an enzyme that in humans is encoded by the CYB5R3 gene. Cytochrome b5 reductase is involved in the transfer of reducing equivalents from the physiological electron donor, NADH, via an FAD domain to the small molecules of cytochrome b5. It’s also heavily involved in many oxidation and reduction reactions, such as the reduction of methemoglobin to hemoglobin.[8] Of the two forms of NADH-cytochrome b5 reductase, the membrane-bound form exists mainly on the cytoplasmic side of the endoplasmic reticulum and functions in desaturation and elongation of fatty acids, in cholesterol biosynthesis, and in drug metabolism. The erythrocyte form is located in a soluble fraction of circulating erythrocytes and is involved in methemoglobin reduction. Mutations in the CYB5R3 gene cause methemoglobinemia types I and II. This is a rare autosomal recessive disease due to a deficiency of isoform of NADH-cytochrome b5 reductase.