{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CRB2 is a Crumbs‐family protein that plays multifaceted roles as a regulator of apico–basal polarity and tissue morphogenesis in diverse organ systems. At its core, CRB2 functions as an organizer of apical membrane identity through its transmembrane form—with additional secreted isoforms—thereby influencing cell–cell adhesion and signaling. In the developing and mature retina, CRB2 is expressed in photoreceptors, Müller glial cells, and the retinal pigment epithelium, where it is essential for proper lamination, maintenance of adhesion, and suppression of inappropriate progenitor expansion; its loss or mutation leads to retinal disorganization and degeneration, modeling conditions such as retinitis pigmentosa and Leber congenital amaurosis (3,4,17).\n\n In the kidney, CRB2 is a crucial determinant of podocyte architecture and function. It governs foot process arborization, slit diaphragm formation, and the correct trafficking of key structural proteins. Mutations in CRB2 have been linked to steroid‐resistant nephrotic syndrome and the development of focal segmental glomerulosclerosis, as evidenced by both human genetic studies and experimental investigations in zebrafish and mouse models (2,12,16,18).\n\n During embryogenesis, CRB2 is indispensable for maintaining epithelial polarity. In the early embryo and developing cortex, loss of CRB2 disrupts the apical polarity complex and impairs processes such as epithelial–to–mesenchymal transition and neural progenitor proliferation and differentiation, resulting in cortical abnormalities (5,6,8,9). Moreover, CRB2 can modulate gamma‐secretase activity by binding to its complex and thereby inhibiting the generation of amyloid‐beta peptides, a function that may have broader neuroprotective implications (7).\n\n Additional roles for CRB2 have been uncovered in specialized tissues. In retinal pigment epithelium, CRB2 localizes to tight junctions where it collaborates with other Crumbs proteins to sustain barrier integrity (14), and in the developing neurovascular environment it indirectly regulates the organization of deep vascular networks via control of neuroglial expression of angiogenic factors (15). CRB2 is also implicated in ciliogenesis, with mutations contributing to ciliopathy syndromes that can include cerebral ventriculomegaly and other systemic anomalies (10), while emerging evidence points to its involvement in the differentiation of pancreatic progenitors through regulatory interactions with enhancers of cell polarity genes (13).\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies demonstrate that CRB2 is a multifunctional polarity protein whose diverse roles in cell adhesion, tissue organization, and signal modulation are critical for normal retinal, renal, neural, and possibly pancreatic development and function"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Celso Henrique Alves, Alicia Sanz Sanz, Bokyung Park, et al. 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