Gap junctions are formed by a hexameric group of proteins called connexions for the transport of low molecular weight proteins from cell to cell. Connexins, which are present in all metazoan organisms, serve diverse functions ranging from control of cell growth and differentiation to electric conduction in excitable tissues. Several mammalian cells with malignant phenotypes exhibit decreased connexin expression and gap junction communication. The pannexin gene family encodes a second class of putative gap junction proteins. Pannexins are highly conserved in invertebrates and mammals, indicating the importance of their gap junctional coupling function. Mammalian Pannexin-1 and Pannexin-3 are closely related, while Pannexin-2 is more distantly related. Pannexin-2 is a transmembrane protein expressed in the central nervous system that is unable to assemble in homomeric channels but forms heteromeric channels with Pannexin-1.