TJP1 (tight junction protein 1, also called zonula occludens-1 or ZO-1) is a scaffolding protein that links tight junction transmembrane proteins such as claudins and occludin to the actin cytoskeleton, forming a multistranded condensate that elongates around the apical membrane to create a tight junction belt. This belt limits paracellular transport and maintains the barrier between apical and basolateral plasma membrane domains in epithelial and endothelial cells. Beyond junction assembly, TJP1 plays critical roles in epithelial polarization, cell migration, and mitotic spindle orientation independent of its barrier function—a 2021 study demonstrated that mice lacking intestinal epithelial TJP1 remained initially healthy but showed defective mucosal repair due to impaired mitotic spindle orientation and Wnt signaling upregulation 1. Pathogenic TJP1 variants have been identified in arrhythmogenic cardiomyopathy and dilated cardiomyopathy 2, while disruption of TJP1 in pluripotent stem cells alters gastrulation patterning and increases differentiation toward primordial germ cells 3. In cancer contexts, reduced TJP1 mRNA stability promotes nasopharyngeal carcinoma cell migration and invasion 4, and SARS-CoV-2 proteins interact with TJP1 through conserved PDZ-binding motifs, potentially disrupting viral immune evasion mechanisms 5. TJP1 dysfunction has been implicated in inflammatory bowel disease, where reduced expression correlates with impaired mucosal healing.