Drosophila DLG (Discs Large Tumor Suppresser Protein) is a component of septate junctions, and disruption of its gene leads to over growth of imaginal discs. Homologs of Drosophila DLG recently isolated from mammalian tissue have been classified as members of the MAGUK (Membrane Associated GUanylate Kinase) superfamily of proteins. Using a modified RT-PCR method applied to rat tissues, we have isolated cDNA clones encoding a novel MAGUK family member that we have named rDLG6. Immunoblot and immunohistochemical analyses revealed that rDLG6 protein is predominantly expressed in brain. GST pull-down assays showed that the PDZ domain of rDLG6 protein binds to the C-terminus of the AMPA (α-Amino-3-hydroxy-5-Methyl-isoxazole-4-Propionic Acid) receptor GluR2 subunit.