{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CRISPLD2 is a secreted protein belonging to the CAP superfamily that has emerged as a multifunctional modulator in both developmental and immune‐regulated processes. Genetic studies in diverse populations have repeatedly associated variation in the CRISPLD2 gene with nonsyndromic cleft lip with or without cleft palate (NSCLP), and detailed expression analyses demonstrate that CRISPLD2 is actively expressed in craniofacial tissues during embryogenesis—suggesting it is important for neural crest cell migration and tissue patterning (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": " Notably, while multiple investigations support its pathogenic involvement in NSCLP, some studies in specific populations have not confirmed this association."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In parallel, CRISPLD2 functions as an LPS‐binding protein with potent anti‐inflammatory properties. In vitro and in vivo data indicate that CRISPLD2 binds lipopolysaccharide with high affinity—comparable to that of soluble CD14—thereby preventing LPS binding to target cells and attenuating LPS‐induced production of proinflammatory cytokines. This LPS‐scavenging activity confers protection in animal models of endotoxin shock and modulates HMGB1‐triggered cytokine release."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "15"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, CRISPLD2—also known as Lgl1 in some contexts—is essential for proper lung development. Its expression by lung fibroblasts is critical for mesenchymal–epithelial interactions that drive alveogenesis, and reduced CRISPLD2 levels are linked to defects in lung branching as well as increased local inflammation in models of bronchopulmonary dysplasia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, CRISPLD2 expression in the endometrium is under progesterone regulation, and its dysregulation has been implicated in the pathogenesis of endometriosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies delineate CRISPLD2 as a multifunctional protein that contributes to craniofacial morphogenesis and lung tissue homeostasis while acting as an endogenous modulator of inflammatory responses. Its dual role in development and inflammation may have broad implications for understanding congenital malformations such as NSCLP, as well as inflammatory conditions including sepsis and lung injury.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brett T Chiquet, Andrew C Lidral, Samuel Stal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRISPLD2: a novel NSCLP candidate gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddm176"}], "href": "https://doi.org/10.1093/hmg/ddm176"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17616516"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17616516"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Brett T Chiquet, Robin Henry, Amber Burt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nonsyndromic cleft lip and palate: CRISPLD genes and the folate gene pathway connection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Birth Defects Res A Clin Mol Teratol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/bdra.20737"}], "href": "https://doi.org/10.1002/bdra.20737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21254358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21254358"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ariadne Letra, Renato Menezes, Margaret E Cooper, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cleft Palate Craniofac J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1597/09-227"}], "href": "https://doi.org/10.1597/09-227"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20815724"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20815724"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xi Shen, Rui-Min Liu, Lan Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The CRISPLD2 gene is involved in cleft lip and/or cleft palate in a Chinese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Birth Defects Res A Clin Mol Teratol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/bdra.20840"}], "href": "https://doi.org/10.1002/bdra.20840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21800413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21800413"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Ana Camila Messetti, Renato Assis Machado, Carine Ervolino de Oliveira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Brazilian multicenter study of association between polymorphisms in CRISPLD2 and JARID2 and non-syndromic oral clefts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Oral Pathol Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jop.12470"}], "href": "https://doi.org/10.1111/jop.12470"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27328068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27328068"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Brett T Chiquet, Qiuping Yuan, Eric C Swindell, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of Crispld2 in zebrafish identifies a novel network for nonsyndromic cleft lip with or without cleft palate candidate genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41431-018-0192-5"}], "href": "https://doi.org/10.1038/s41431-018-0192-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29899370"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29899370"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ainiwaer Mijiti, Wang Ling, Abudukelimujiang Maimaiti, et al. 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