CYB5R3,also named as DIA1 and B5R,belongs to the flavoprotein pyridine nucleotide cytochrome reductase family. It plays an essential role in the mitochondrial metabolism by its contribution to cellular redox homeostasis. Overstimulation of CYB5R3 associated with lipid rafts can account for the overshot of plasma membrane-focalized superoxide anion production that triggers the entry of CGN in the irreversible phase of apoptosis.