||Glyceraldehyde-3-phosphatedehydrogenase (GAPDH; EC 188.8.131.52) catalyzes an important energy-yielding step in carbohydrate metabolism, the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and nicotinamideadenine dinucleotide (NAD). The enzyme is present in such widely separated forms as man, lobster, and E. coli. Its rate of evolutionary change is one of the slowest known. Recent evidence demonstrates that mammalian GAPDH displays a number of diverse activities unrelated to its glycolytic function. These include its role in membrane fusion, microtubule bundling, phosphotransferaseactivity, nuclear RNA export, DNA replication and DNA repair. These new activities may be related to the subcellular localization and oligomeric structure of GAPDH in vivo. Furthermore, other investigations suggest that GAPDH is involved in apoptosis, age-relatedneurodegenerative disease, prostate cancer and viral pathogenesis. Intriguingly, GAPDH is also a unique target of nitric oxide. Recently GAPDH has been shown to be a common target of a number of compounds with potent antiproliferative activities and thus a potential target for chemotherapeutic intervention.