Epithelial tight-junction and immune surface proteins

Epithelial tight-junction and immune surface proteins refers to a group of transmembrane proteins that constitute the apical-most junctional complex in epithelial and endothelial cells, while also serving as signaling molecules and receptors on the surface of immune cells. Key members include the Claudin family (e.g., Claudin-18.2, Claudin-6), Occludin, and Junctional Adhesion Molecules (JAMs, such as JAM-A). These proteins are essential for maintaining the physical barrier between tissue compartments (the gate function) and regulating the movement of lipids and proteins within the cell membrane (the fence function). In many cancers, these proteins are overexpressed or mislocalized, making them attractive targets for monoclonal antibodies, bispecific T-cell engagers, and CAR-T therapies. For instance, Claudin-18.2 is a major target in gastric and pancreatic cancers, while JAM-A is involved in leukocyte transmigration and is being explored as a target in both oncology and inflammatory diseases. This target name is considered a descriptive category rather than a single canonical molecule.

Other names

Tight junction proteinsTJ proteinsClaudinsJunctional Adhesion MoleculesJAMsEpithelial surface antigensEpithelial cell adhesion molecule (EpCAM)

Drugs targeting these proteins typically work by binding to extracellular loops to induce antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or by disrupting the physical barrier to enhance drug delivery and modulate immune cell infiltration.