Neuroendocrine-Dlg (NE-Dlg) is a member of the discs-large-related (DLG) subfamily of the membrane-associated guanylate kinase-related protein family. Based on evidence from model systems, this protein appears to be critical for synaptogenesis, acting as a site-specific organizational center for integral membrane proteins and their downstream signaling molecules associated with the cytoskeleton. NE-Dlg also directly interacts with the colorectal tumor suppressor adenomatous polyposis coli, suggesting that it may play a role in regulating cell proliferation in epithelial cells. To explore the genetic control of NE-Dlg, we developed a physical map of the chromosome region containing DLG3, the locus encoding NE-Dlg. Using human-hamster radiation hybrid mapping panels, we mapped DLG3 to Xq13.1 and established a sequence-tagged site marker map of the surrounding region. We then developed a yeast artificial chromosome (YAC) contig for this region. Encompassing approximately 2.0 Mb contained within five overlapping YACs, this contig also includes the dystonia-parkinsonism syndrome (DYT3) locus. The close proximity of DLG3 to the DYT3 region suggests that the gene encoding NE-Dlg is a candidate locus for this neurological disorder.