{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Claudin‐19, encoded by the CLDN19 gene, is an integral tight junction protein that plays a dual role in maintaining renal and retinal function. In the kidney, claudin‐19 is highly expressed in renal tubules where it partners with claudin‐16 to form heteromeric complexes in the tight junctions of the thick ascending limb of Henle. This complex is essential for creating cation‐selective paracellular channels that mediate the reabsorption of magnesium and calcium; disruption of claudin‐19 (by mutations or knockdown) impairs ion selectivity, leading to renal magnesium loss, hypercalciuria, and consequent nephrocalcinosis and chronic renal failure."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its renal role, claudin‐19 is critically involved in the development and integrity of the retina. High retinal expression of claudin‐19 is necessary for establishing proper cell–cell adhesion and barrier properties in retinal pigment epithelium. Its deficiency or mutation is associated with severe ocular abnormalities such as myopia, nystagmus, macular coloboma, and other visual deficits."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, detailed clinical studies and genetic analyses have linked CLDN19 mutations with a variant of familial hypomagnesemia with hypercalciuria and nephrocalcinosis that includes ocular involvement. The mutations disrupt claudin‐19’s ability to be correctly trafficked to and assembled within tight junctions, thereby compromising its function in both the kidney and retina. Additionally, regulation of CLDN19 expression has been shown to involve transcription factors such as Sp1, which bind to its promoter region to drive expression in kidney cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, claudin‐19 is a pivotal mediator of paracellular transport, ensuring proper reabsorption of divalent cations in the kidney while also contributing to the structural and functional integrity of the retinal pigment epithelium. Disruption of claudin‐19 function leads to a multisystem phenotype characterized by renal ion imbalance and ocular defects.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Martin Konrad, Andre Schaller, Dominik Seelow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/508617"}], "href": "https://doi.org/10.1086/508617"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17033971"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17033971"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jianghui Hou, Aparna Renigunta, Antonio S Gomes, et al. 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