{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nST8SIA2 encodes a polysialyltransferase that catalyzes the addition of long, negatively charged polysialic acid chains onto glycoproteins – most notably the neural cell adhesion molecule (NCAM). This polysialylation modulates NCAM‐mediated cell–cell adhesion, thereby regulating key processes in neural development such as neuronal migration, synaptic plasticity, and the formation of neural networks. Biochemical analyses have shown that ST8SIA2, often acting in concert with another polysialyltransferase (ST8SIA4), determines not only the extent but also the specific structural quality of the polySia chains on NCAM. The proper synthesis of these chains is critical because any alteration, including those resulting from pathogenic mutations, can cause significant changes in the binding of neuromodulators (e.g., dopamine and BDNF) and ultimately impact neural function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies across diverse populations have implicated ST8SIA2 as a susceptibility gene for several neuropsychiatric disorders, including bipolar disorder, schizophrenia, and autism spectrum disorder. Multiple genome‐wide association studies and candidate gene analyses have identified risk variants that affect ST8SIA2 expression and enzymatic function, thereby disrupting early neuronal network formation and altering white matter microstructure. Moreover, alterations in ST8SIA2 have been associated with changes in circadian and seasonal behavior, reinforcing its role in the regulation of the neural circuitry underlying mood and cognitive function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in neurodevelopment and psychiatric risk, ST8SIA2 has been implicated in other physiological contexts. For instance, genetic variation in a locus near ST8SIA2 correlates with the degree of weight loss following Roux-en-Y gastric bypass surgery, suggesting a role in energy balance and metabolic regulation. In addition, increased expression of ST8SIA2 in cancer-associated fibroblasts and tumor cells has been linked to enhanced invasion and metastasis in lung cancers, while altered polySia synthesis in malignant cells may contribute to tumor progression. These findings highlight the multifunctional impact of ST8SIA2, from mediating cell adhesion in the developing brain to influencing disease processes in adult tissues."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kiyohiko Angata, Misa Suzuki, Minoru Fukuda "}, {"type": "b", "children": [{"type": "t", "text": "ST8Sia II and ST8Sia IV polysialyltransferases exhibit marked differences in utilizing various acceptors containing oligosialic acid and short polysialic acid. The basis for cooperative polysialylation by two enzymes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M204632200"}], "href": "https://doi.org/10.1074/jbc.M204632200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12138100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12138100"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Deirdre A Foley, Kristin G Swartzentruber, Karen J Colley "}, {"type": "b", "children": [{"type": "t", "text": "Identification of sequences in the polysialyltransferases ST8Sia II and ST8Sia IV that are required for the protein-specific polysialylation of the neural cell adhesion molecule, NCAM."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M809696200"}], "href": "https://doi.org/10.1074/jbc.M809696200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19336400"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19336400"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ryo Isomura, Ken Kitajima, Chihiro Sato "}, {"type": "b", "children": [{"type": "t", "text": "Structural and functional impairments of polysialic acid by a mutated polysialyltransferase found in schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.221143"}], "href": "https://doi.org/10.1074/jbc.M111.221143"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21464126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21464126"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Airi Mori, Masaya Hane, Yuki Niimi, et al. 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