Rapid progress in the identification and characterization of axon guidance molecules and their receptors has left the field poised to explore the intracellular mechanisms by which signals are transduced into growth cone responses. The TUC (TOAD/Ulip/CRMP) family of proteins has emerged as a strong candidate for a role in growth cone signaling. The TUC family members reach their highest expression levels in all neurons during their peak periods of axonal growth and are strongly down‐regulated afterward. When axonal regrowth in the adult is triggered by axotomy, TUC‐4 is reexpressed during the period of regrowth. Mutations in unc‐33, a homologous nematode gene, lead to severe axon guidance errors in all neurons. Furthermore, the TUC family is required for the growth cone–collapsing activity of collapsin‐1. An important role for the TUC family is also suggested by its high degree of interspecies amino acid sequence identity, with the rat TUC‐2 protein showing 98% identity with its chick ortholog and 89% identity with its Xenopus ortholog. Information gained from the study of the TUC family will be of key importance in understanding how growth cones find their targets. © 1999 John Wiley & Sons, Inc. J Neurobiol 41: 158–164, 1999