The Fasciculation and Elongation Factor 1 (FEZ1) is a mammalian orthologue of the Caenorhabditis elegans protein UNC-76, which is necessary for axon growth in that nematode. In different published studies FEZ1 has been found to interact with PKCzeta, DISC1, the agnoprotein of the human polyomavirus JC virus and E4B, an U-box-type ubiquitin-protein isopeptide ligase. We previously reported that FEZ1 and its paralogue FEZ2 are proteins that interact with NEK1, a protein kinase involved in polycystic kidney disease and DNA repair mechanisms at the G2/M phase of the cell cycle. To obtain more information about the possible functional context of FEZ1 we set out to use this protein itself as a bait in a yeast two-hybrid assay and screened a human fetal brain cDNA library for potential interacting proteins. We found that FEZ1 interacts with itself and with another 15 proteins. The 13 interacting proteins of known functions take either part in transcription regulation and chromatin remodeling (6), the regulation of neuronal cell development (2), cellular transport mechanisms (3), or participate in apoptosis (2). We were able to confirm eight of the observed interactions by in vitro pull down assays with recombinant fusion proteins. The confirmed interacting proteins include FEZ1 itself and three transcription controlling proteins (SAP30L, DRAP1 and BAF60a). In mapping studies by yeast two-hybrid assays we found that the C-terminal region of FEZ1, and especially its coiled-coil region, are involved in its dimerization, its hetero-dimerization with FEZ2 as well as in the interaction with ten of the identified interacting proteins. The FEZ1 dimerization also was verified by size exclusion chromatography analysis. Our results give further support to the previous speculation of the functional involvement of FEZ1 in neuronal development. However, our new finding that FEZ1 interacts with nuclear proteins, six of which are functionally involved in transcription regulation and chromatin remodeling, opens the intriguing new possibility that FEZ1 may in addition to the previous predicted functions also have regulatory functions in the nucleus.