TJP1 (tight junction protein 1, also called ZO-1) is a critical scaffolding protein that links tight junction transmembrane proteins such as claudins and occludin to the actin cytoskeleton 12. It forms multistranded condensates that create the tight junction belt, establishing a selectively permeable epithelial barrier that limits paracellular transport and maintains apical-basolateral membrane domain separation 3. Beyond barrier function, TJP1 has surprising junction-independent roles. It associates with centrioles and mitotic spindle poles, where it is essential for proper spindle orientation and mitotic progression; loss of TJP1 causes mitotic catastrophe and defective epithelial proliferation 4. TJP1 also regulates Wnt signaling and is critical for mucosal repair responses to injury 4. In developing tissues, TJP1 disruption impairs gastrulation patterning by allowing enhanced BMP4 signaling 5. Clinically, TJP1 expression is reduced in inflammatory bowel disease patients 4. TJP1 stability is regulated by PEAK1-mediated protection from autophagy-mediated degradation, and PEAK1 loss increases intestinal permeability and exacerbates colitis 6. In cancer contexts, TJP1 supports cell aggregation and sarcoma genesis, suggesting therapeutic potential through TJP1 targeting 7. TJP1 dysregulation is also implicated in recurrent spontaneous abortion through the circFBXW4/miR-324-3p/TJP1 axis 8.