PATJ (PALS1-associated tight junction protein) is a scaffolding protein essential for epithelial cell polarity and tight junction formation 12. It facilitates the localization of proteins to the cell membrane and connects apical and lateral tight junction components, stabilizing the Crumbs3 complex and regulating spatial concentration of junction proteins 3. PATJ positively regulates cell migration and microtubule elongation, potentially through facilitating localization of polarity regulators at cell leading edges 4. Beyond structural roles, PATJ functions in cellular stress responses and immune activation. PATJ regulates the YAP1 signaling pathway and cell proliferation, with deletion causing transcriptional reprogramming affecting vascular development and metabolism genes 5. The PATJ/MPZ-1 homolog protects against hypoxic stress in neurons, critical for ischemic stroke recovery 5. Additionally, PATJ's PDZ domains facilitate immunological synapse formation between T cells and antigen-presenting cells, promoting T cell activation and enhancing CAR-T cell cytotoxicity 6. Clinically, PATJ variants associate with stroke outcome: low-frequency variants (rs76221407) correlate with worse functional recovery at 3 months post-stroke 7. PATJ downregulation after ischemic stroke promotes endothelial-to-mesenchymal transition through Hippo/Notch/PI3K signaling, paradoxically associated with functional independence 8. PATJ also associates with daytime napping behavior and cardiometabolic phenotypes 9.