{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nLRRC7, which encodes the scaffolding protein densin‐180, is best recognized for its critical role at glutamatergic synapses in the brain. In neurons, densin‐180 serves as an organizational hub in the postsynaptic density by linking cytoskeletal elements with key signaling molecules—including delta‐catenin, Ca2+/calmodulin‐dependent protein kinase II (CaMKII), and protein phosphatase 1—to modulate receptor phosphorylation, synaptic signaling, and cell polarity. Moreover, a splice variant of LRRC7 is expressed ubiquitously, contrasting with the more brain‐restricted densin‐180, and suggesting additional cellular functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nLRRC7 is also prominently expressed in kidney podocytes where densin localizes at the slit diaphragm—a key structure of the glomerular filtration barrier. In this setting, densin interacts with proteins such as nephrin, beta‐catenin, and alpha‐actinin‐4 to help establish and maintain cell–cell contacts and structural integrity. Genetic association studies further implicate LRRC7 in podocyte function and diabetic nephropathy, underscoring its role in preserving cell polarity and podocyte adhesion."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond the brain and kidney, LRRC7 expression is observed in other tissues including pancreatic islet cells and Sertoli cells of the testis, hinting at roles in cell adhesion and junction formation. Notably, autoantibody responses against densin have been detected in type 1 diabetes, while genome‐wide investigations have linked LRRC7 variants with neurodevelopmental and behavioral disorders such as intellectual disability, autism, and attention-deficit/hyperactivity disorder. These findings collectively point to LRRC7 as a multifunctional protein, integral to synaptic organization, renal filtration, and broader aspects of human development and disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ichiro Izawa, Miwako Nishizawa, Kazuhiro Ohtakara, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Variants in LRRC7 lead to intellectual disability, autism, aggression and abnormal eating behaviors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-024-52095-x"}], "href": "https://doi.org/10.1038/s41467-024-52095-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39256359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39256359"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Heikki Ahola, Eija Heikkilä, Eva Aström, et al. 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