The discs large (dlg) tumor suppressor gene was first identified in Drosophila through genetic analysis of germline mutations. Several mammalian homologs were subsequently identified and categorized into a protein family designated MAGUK (membrane-associated guanylate kinase homolog). The mammalian homolog of dlg, SAP 97, is also known as hdlg-1 (human) and NE-dlg (neuronal and endocrine). The rat synaptic protein SAP 90 (also designated PSD-95) also shares homology with these proteins. MAGUKs are localized at the membrane-cytoskeleton interface and contain several distinct domains which suggest a role for these proteins in intracellular signal transduction. Interaction of hdlg-1 and NE-dlg with the tumor suppresor protein APC suggest that MAGUK proteins may also play a role in regulation of growth.