Discs large MAGUK scaffold protein 5 (DLG5)

Discs large MAGUK scaffold protein 5 (DLG5) is a member of the membrane-associated guanylate kinase (MAGUK) protein family, functioning predominantly as a molecular scaffold at cell-cell contact sites[1][3][5]. DLG5 contains PDZ, SH3, GUK, coiled-coil, and CARD domains, allowing it to interact with a wide variety of proteins—most notably components of adherens junctions (such as β-catenin and N-cadherin), the cytoskeleton, polarity complexes, and signaling receptors[1][2]. It is highly conserved in animals and localizes to the plasma membrane and adherens junctions, where it orchestrates the assembly and stabilization of protein complexes essential for epithelial polarity and tissue architecture[1][3][5][6]. In development and cancer, DLG5 regulates several essential processes, including cell proliferation, migration, and differentiation, mainly through modulation of the Hippo signaling pathway and by maintaining junctional integrity[1][2][4][5]. It acts as a negative regulator of Hippo signaling by scaffolding and inhibiting key kinases (e.g., MST1/2), influencing downstream transcription important for organ size and growth[1]. DLG5 also participates in the Sonic Hedgehog (Shh) pathway in certain tumor contexts, such as glioblastoma, where it promotes tumor cell viability and migration through stabilization of Shh pathway effectors[4]. Genetic mutations or dysregulation of DLG5 have been associated with multiple diseases, ranging from epithelial morphogenesis defects, inflammatory bowel diseases (e.g., Crohn’s disease), to various cancers[2][3][4]. Despite its involvement in cellular signaling pathways, DLG5 is not currently recognized as a direct therapeutic drug target (such as a receptor, enzyme, transporter), and there are no known approved drugs that specifically target DLG5[3][4]. Overall, DLG5 is primarily considered a scaffold/adaptor protein crucial for epithelial cell polarity and tissue organization, indirectly influencing signaling pathways and disease mechanisms rather than serving as a conventional drug target.

Other names

Discs large homolog 5DLG5Discs large 5