Multiple roles for glyceraldehyde-3-phosphate dehydrogenase (GAPDH) have been recently appreciated. GAPDH is found in the particulate fractions, such as the nucleus, the mitochondria, and the small vesicular fractions. GAPDH gene expression is specifically increased during programmed neuronal cell death. When cells are exposed to various stressors, dynamic subcellular re-distribution of GAPDH occurs. GAPDH is also involved in various diseases, especially neurodegenerative disorders and cancers. As a membrane protein, GAPDH functions in endocytosis; in the cytoplasm, it is involved in the translational control of gene expression; in the nucleus, it functions in nuclear tRNA export, in DNA replication, and in DNA repair.