DLG1 is an essential multidomain scaffolding protein that organizes proteins at discrete plasma membrane domains to maintain epithelial cell polarity and barrier function 1. Structurally, DLG1 functions as a core component of the Scribble polarity complex and operates upstream of multiple cellular processes including adherens junction assembly, cell-cell adhesion maintenance, and tight junction integrity 1. Mechanistically, DLG1 regulates ciliary protein trafficking by controlling SDCCAG3 and IFT20-mediated localization of polycystin-2 to primary cilia in kidney epithelial cells 2. In immune cells, DLG1 is essential for dendritic cell maturation, promoting CD83 upregulation and IL-6 production, thereby facilitating downstream T cell activation 3. DLG1 shows strong expression during early kidney development with progressive decline, suggesting critical roles in nephrogenesis 4. Disease relevance is substantial: DLG1 dysfunction contributes to Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), as the p.T489R variant impairs ciliary protein trafficking 2. Altered DLG1 expression and subcellular localization occur across multiple pathologies including cancers, neurological, and immunological disorders 5. In oropharyngeal squamous cell carcinomas, DLG1 relocalization from cell-cell contacts to cytoplasm correlates with malignant progression 6. Emerging evidence indicates circDlg1 regulates microglial neuroinflammation in Alzheimer's disease through PDE4B-mediated cAMP signaling 7.