{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC44A1, also known as choline transporter‐like protein 1 (CTL1), is a membrane protein that mediates cellular choline uptake essential for the synthesis of membrane phospholipids (eg, phosphatidylcholine) and the neurotransmitter acetylcholine. Experimental studies in muscle cells, breast cancer cells, hepatocytes, and neural cell lines have shown that SLC44A1 is expressed not only on the plasma membrane but also in intracellular compartments such as mitochondria, where it supports key metabolic processes including choline oxidation and fatty acid synthesis. Its activity is sensitive to inhibition by hemicholinium‐3 and is regulated by choline availability, as lower choline levels down‐regulate its expression and choline uptake."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAberrations in SLC44A1 function and expression have been linked to diverse pathological states. In cancer cells—such as in lung carcinoma—the transporter’s activity supports rapid cell proliferation by ensuring sufficient substrate for phospholipid biosynthesis and even autocrine acetylcholine production, while a fusion between SLC44A1 and PRKCA has been identified as a diagnostic marker in papillary glioneuronal tumors. Moreover, mutations or reduced expression of SLC44A1 have been associated with neurodegenerative disorders and conditions like postural orthostatic tachycardia syndrome, where impaired choline uptake leads to disturbances in membrane homeostasis and mitochondrial function. Its expression is also critical in the placenta to guarantee an adequate choline supply to the developing fetus, and emerging evidence indicates that vitamin D signaling may modulate SLC44A1 expression; finally, specific single nucleotide polymorphisms in SLC44A1 have been linked to improved cognition in children following prenatal alcohol exposure."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its established role in choline import, recent studies have expanded the functional repertoire of SLC44A1 by demonstrating its involvement in the transport of ethanolamine—a substrate for de novo phosphatidylethanolamine synthesis via the Kennedy pathway—thereby linking its activity to broader aspects of membrane lipid homeostasis. Its expression is subject to nuanced transcriptional regulation and altered intracellular trafficking, with protein kinase C signaling shown to enhance its cell-surface levels in hepatic cells, and regulation in neural stem cells further underpinning its role in neurodevelopment. These refined regulatory mechanisms, as well as promoter and splice variant studies, underscore the critical importance of SLC44A1 not only in maintaining fundamental cellular functions but also as a potential target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "18"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Vera Michel, Marica Bakovic "}, {"type": "b", "children": [{"type": "t", "text": "The solute carrier 44A1 is a mitochondrial protein and mediates choline transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.08-121491"}], "href": "https://doi.org/10.1096/fj.08-121491"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19357133"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19357133"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Morgan D Fullerton, Laura Wagner, Zongfei Yuan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired trafficking of choline transporter-like protein-1 at plasma membrane and inhibition of choline transport in THP-1 monocyte-derived macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Cell Physiol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpcell.00255.2005"}], "href": "https://doi.org/10.1152/ajpcell.00255.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16319125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16319125"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Toshimichi Nakamura, Ryohei Fujiwara, Naoki Ishiguro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of choline transporter-like proteins, CTL1 and CTL2, in glucocorticoid-induced acceleration of phosphatidylcholine synthesis via increased choline uptake."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Pharm Bull (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1248/bpb.33.691"}], "href": "https://doi.org/10.1248/bpb.33.691"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20410607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20410607"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Tomoko Yamada, Masato Inazu, Hirohisa Tajima, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional expression of choline transporter-like protein 1 (CTL1) in human neuroblastoma cells and its link to acetylcholine synthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Int (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuint.2010.12.011"}], "href": "https://doi.org/10.1016/j.neuint.2010.12.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21185344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21185344"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Vera Hedtke, Marica Bakovic "}, {"type": "b", "children": [{"type": "t", "text": "Choline transport for phospholipid synthesis: An emerging role of choline transporter-like protein 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Biol Med (Maywood) (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/1535370219830997"}], "href": "https://doi.org/10.1177/1535370219830997"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30776907"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30776907"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Vera Michel, Marica Bakovic "}, {"type": "b", "children": [{"type": "t", "text": "The ubiquitous choline transporter SLC44A1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cent Nerv Syst Agents Med Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/187152412800792733"}], "href": "https://doi.org/10.2174/187152412800792733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22483272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22483272"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Masato Inazu, Tomoko Yamada, Nobuo Kubota, et al. 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