The doublecortin-like (DCX) domains serve as protein-interaction platforms. DCXtandem domains appear in the product of the X-linked doublecortin (DCX) gene, inretinitis pigmentosa –1 (RP1), as well as in other gene products. Mutations in the humanDCX gene are associated with abnormal neuronal migration, epilepsy, and mentalretardation; mutations in RP1 are associated with a form of inherited blindness, whileDCDC2 has been associated with dyslectic reading disabilities. Motivated by the possibleimportance of this gene family, a thorough analysis to detect all family members in themouse was conducted. The DCX-repeat gene superfamily is composed of elevenparalogs, and we cloned the DCX domains from nine different genes. Our studyquestioned which functions attributed to the DCX domain, are conserved among thedifferent members. Our results suggest that the proteins with the DCX-domain haveconserved and unique roles in microtubule regulation and signal transduction. All thetested proteins stimulated microtubule assembly in vitro. Proteins with tandem repeatsstabilized the microtubule cytoskeleton in transfected cells, while those with singlerepeats localized to actin-rich subcellular structures, or the nucleus. All tested proteins interacted with components of the JNK/MAP-kinase pathway, while only a subsetinteracted with Neurabin 2, and a non-overlapping group demonstrated actin association.The sub-specialization of some members due to confined intracellular localization, andprotein interactions may explain the success of this superfamily.