To make a gap junction, cells assemble six plasma-membrane connexin proteins into a hemichannel; in turn, two hemichannels on adjacent cells dock to form a complete intercellular channel. Mutations in the cytoplasmic N-terminal domain of connexins affect the physiological properties of hemichannels and give rise to several inherited diseases, but the molecular basis of these effects has been unclear. Now, Eric Beyer and colleagues (p. 2744) investigate the role of the 23-amino-acid N-terminus of connexin37 (CX37) in hemichannel formation and function. The authors show that N-terminal deletion mutants of CX37 can form gap-junction plaques in transiently transfected HeLa cells, provided that nine or more amino acids are present. By contrast, none of the tested mutants allow the intercellular transfer of neurobiotin, whereas wild-type CX37 does; moreover, the mutants do not form conducting hemichannels in Xenopus oocytes. A full-length CX37 mutant, in which N-terminal residues 2-8 are replaced by alanines, forms plaques but, similar to the deletion mutants, does not restore function. Thus, many N-terminal connexin residues are dispensable for the formation of plaques (and for membrane insertion and trafficking, which precede plaque formation). Instead, the authors conclude, the N-terminus has an essential role in hemichannel gating.