{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPALS1 is a membrane‐associated guanylate kinase protein that plays a central role in establishing and maintaining epithelial cell polarity. It localizes prominently at tight junctions through interactions mediated by its L27 and PDZ domains, assembling evolutionarily conserved multiprotein complexes that include PATJ and Crumbs proteins. These interactions not only target PALS1 to the junctional membrane but also contribute to the assembly and stabilization of apical–basal polarity, as revealed by studies on epithelial cells and Drosophila models. Structural insights into its L27‐mediated complex formation further underscore its scaffolding function in organizing cell junction components."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond epithelia, PALS1 contributes critically to polarized tissue development and function. In myelinating Schwann cells, it is required for the proper radial and longitudinal extension of the myelin sheath by regulating membrane protein trafficking, while in the retina, its absence disrupts retinal pigment epithelium structure and photoreceptor cell layering. Moreover, emerging studies have begun to address its expression in immune cells, suggesting potential roles in T cell activation and polarization during immune responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPALS1 is also a key target in pathological conditions. Viral envelope proteins from SARS‐CoV and SARS‐CoV‑2 exploit its PDZ domain through specific PDZ‐binding motifs, leading to mislocalization of PALS1 away from cell–cell junctions and subsequent disruption of epithelial integrity. Additionally, aberrations in PALS1 expression or its involvement in gene fusion events (such as the MPP5-FAM71D fusion) have been linked to increased cell migration and metastasis in cancers. Such dysregulation appears to promote enhanced Arf6 and Rac1 signaling, thereby facilitating cancer cell invasion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael H Roh, Olga Makarova, Chia-Jen Liu, et al. 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