Recent evidence indicates new, intriguing roles for the glycolytic protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in fundamental mammalian cell processes. These include its role in DNA repair, in the translational control of gene expression, in DNA replication and in endocytosis. These findings have the potential to alter our basic understanding of the molecular mechanisms through which human or mammalian cells utilize individual proteins in vital, yet unrelated, cell processes.