The gene unc-76 ( unc , uncoordinated) is necessary for normal axonal bundling and elongation within axon bundles in the nematode Caenorhabditis elegans . The UNC-76 protein and two human homologs identified as expressed sequence tags are not similar to previously characterized proteins and thus represent a new protein family. At least one of these human homologs can function in C. elegans , suggesting that it, like UNC-76, acts in axonal outgrowth. We propose that the UNC-76 protein, which is found in cell bodies and processes of all neurons throughout development, either has a structural role in the formation and maintenance of axonal bundles or transduces signals to the intracellular machinery that regulates axonal extension and adhesion.