{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Galectin-16 (LGALS16) is a unique member of the galectin family that displays several atypical functional and structural features when compared to other prototypical galectins. Structural analyses have demonstrated that, unlike its counterparts, Gal-16 lacks conventional β‐galactoside (lactose) binding due to the replacement of key amino acid residues. This structural divergence is accompanied by its monomeric state and predominant nuclear localization, which in turn suggests functions beyond classical carbohydrate‐mediated cell adhesion. In support of this notion, Gal-16 has been shown to interact with the NF-κB family member c-Rel, implicating it in the regulation of signaling pathways that are crucial for immune function at the maternal–fetal interface."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of placental development, LGALS16 expression is strongly associated with trophoblast differentiation. During human embryonic stem cell differentiation into trophoblast-like cells, upregulation of synctiotrophoblast-specific genes, including LGALS16, is observed alongside the induction of molecular pathways involved in embryo implantation. Such findings suggest that Gal-16 may contribute to establishing or maintaining immune tolerance mechanisms critical for a successful pregnancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Evolutionary studies indicate that placentally expressed galectins, including LGALS16, have emerged through gene duplications and promoter modifications during primate evolution. Dysregulation of this cluster of galectin genes is associated with pregnancy complications such as preeclampsia, which underscores the potential role of Gal-16 in modulating maternal–fetal immune interactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in human placental function, studies in avian models provide further insights. The chicken homolog of LGALS16, known as CG-16, exhibits distinct tissue-specific expression patterns and intracellular distributions during development. Although CG-16 shares some commonalities with human Gal-16, its unique subcellular localization, including mitochondrial association in certain cell types, further suggests that members of this galectin subgroup may perform specialized roles during organogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, the available evidence indicates that LGALS16 encodes a galectin with noncanonical ligand-binding properties whose intracellular distribution and interaction with key transcriptional regulators, such as c-Rel, point to novel roles in regulating immune and developmental processes at the maternal–fetal interface. Its evolutionarily acquired functions, underscored in both human and avian studies, highlight its potential importance in trophoblast differentiation and immune tolerance.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yunlong Si, Yuan Yao, Gabriela Jaramillo Ayala, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human galectin-16 has a pseudo ligand binding site and plays a role in regulating c-Rel-mediated lymphocyte activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Gen Subj (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbagen.2020.129755"}], "href": "https://doi.org/10.1016/j.bbagen.2020.129755"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33011338"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33011338"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "N G Than, R Romero, Y Xu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Temporal and spatial regulation of expression of two galectins during kidney development of the chicken."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Histochem J (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1023/a:1004032428814"}], "href": "https://doi.org/10.1023/a:1004032428814"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10943846"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10943846"}]}]}]}