{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DLG5, a member of the membrane‐associated guanylate kinase (MAGUK) family, encodes a scaffolding protein that is critically important for maintaining epithelial cell polarity, cellular adhesion, and tissue integrity. It localizes at sites of cell–cell contact by linking cytoskeletal components – for example, it interacts with vinexin and beta‐catenin to help organize adherens junction complexes, thereby contributing to proper cytoskeletal organization and polarized signaling (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic studies have revealed that certain variants in DLG5 – particularly the nonsynonymous R30Q substitution – are associated with inflammatory bowel disease (IBD). These associations, which sometimes display complex gene–gene interactions (e.g. with CARD15) and even gender‐specific effects, underscore a role for DLG5 in modulating the epithelial barrier and immune homeostasis in the gut (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its functions in intestinal epithelial maintenance, DLG5 has been implicated in oncogenesis. In several malignancies—including pancreatic ductal adenocarcinoma, breast cancer, glioblastoma, and hepatocellular carcinoma—aberrant DLG5 expression or mislocalization disrupts normal cell polarity and signaling. In these contexts, loss or altered subcellular distribution of DLG5 contributes to deregulated Hippo signaling (with subsequent increases in nuclear YAP levels), as well as enhanced invasive properties through effects on structures such as invadopodia (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies indicate that DLG5 functions as a multifunctional scaffold that not only upholds epithelial architecture but also modulates key signaling pathways. Disruption of its normal activity—whether by genetic variation or misregulation—can contribute both to altered immune responses in the gut, as seen in IBD, and to tumorigenic processes in diverse epithelial cancers.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Monika Stoll, Brit Corneliussen, Christine M Costello, et al. 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