CLDN1 (claudin 1) is a tight junction protein with dual roles in barrier function and disease pathology. Primarily, CLDN1 localizes to cell-cell junctions and regulates paracellular permeability in epithelial and endothelial tissues 1. CLDN1 serves as a co-receptor for hepatitis C virus entry, functioning through a complex with CD81 2, and acts as a receptor for dengue virus 3. In disease contexts, CLDN1 dysregulation drives pathogenic mechanisms across multiple conditions. In colorectal cancer, CLDN1 interacts with EPHA2 tyrosine kinase to promote cancer stemness and chemoresistance through enhanced AKT signaling and CD44 expression 4. LIN28B-mediated upregulation of CLDN1 enhances collective invasion and metastatic liver tumor formation via NOTCH3 activation 5. In primary sclerosing cholangitis, elevated CLDN1 expression correlates with disease progression and pro-inflammatory/pro-fibrotic signaling; CLDN1-specific monoclonal antibodies reduce hepatobiliary fibrosis and cholestasis in mouse models 6. CLDN1 dysregulation also disrupts coronary microvascular integrity, increasing permeability and causing inflammation and fibrosis that impairs cardiac function 7. Clinically, CLDN1 emerges as a therapeutic target. Combined CLDN1, KRT19, and TIMP1 expression analysis shows 85.4% accuracy for thyroid cancer diagnosis 8, while monoclonal antibody targeting shows promise for PSC treatment.