{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC6A20, also known as the sodium‐dependent imino acid transporter 1 (SIT1), plays a central role in the uptake of key amino acids such as L‐proline, hydroxyproline, and glycine across epithelial membranes. Detailed kinetic analyses using intestinal brush border membrane vesicles have shown that the transporter operates via a rapid equilibrium iso‐ordered mechanism, whereby the binding of two Na⁺ ions (and in some cases Cl⁻) to the carrier greatly enhances proline affinity and facilitates its translocation. These experiments delineate the stoichiometry and substrate‐driven conformational changes that underlie efficient imino acid transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn human small intestine, SLC6A20 is found co‐localized with other luminal amino acid transporters and the angiotensin‐converting enzyme 2 (ACE2) receptor, indicating a coordinated role in nutrient uptake and local regulatory signaling. Studies in intestinal biopsies highlight that the expression and distribution of SLC6A20 (together with associated proteins such as B₀AT1) are modulated by treatments that affect the renin–angiotensin system, such as ACE inhibitors and angiotensin receptor blockers. Notably, while this transporter is robustly expressed in adult enterocytes, its mRNA and protein levels are considerably lower or undetectable in the intestine of human newborns, revealing a developmentally regulated expression profile."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its primary biochemical function, genetic association studies have implicated SLC6A20 in various disease states. Polymorphisms in SLC6A20 have been linked to type 2 diabetes susceptibility and, notably, to Hirschsprung’s disease—where specific variants correlate with the severity of aganglionosis and the risk of Hirschsprung-associated enterocolitis. In addition, genome-scale CRISPR screens and eQTL analyses have identified SLC6A20 as a putative causal gene modulating COVID-19 risk, a link that is further reinforced by recent findings suggesting that the transporter may regulate glycine homeostasis and thereby influence proinflammatory cytokine secretion. Collectively, these studies underscore the multifaceted role of SLC6A20 not only in amino acid reabsorption but also in modulating disease processes associated with aberrant transporter function and inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "B R Stevens, E M Wright "}, {"type": "b", "children": [{"type": "t", "text": "Kinetics of the intestinal brush border proline (Imino) carrier."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (1987)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "3571270"}], "href": "https://pubmed.ncbi.nlm.nih.gov/3571270"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Angelika Bröer, Sarojini Balkrishna, Gabor Kottra, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Intestinal IMINO transporter SIT1 is not expressed in human newborns."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00318.2017"}], "href": "https://doi.org/10.1152/ajpgi.00318.2017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30160974"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30160974"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Y Ling, T T W van Herpt, M van Hoek, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genetic variant in SLC6A20 is associated with Type 2 diabetes in white-European and Chinese populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabet Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/dme.12528"}], "href": "https://doi.org/10.1111/dme.12528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24958070"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24958070"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jin Sol Lee, Jung-Tak Oh, Jeong-Hyun Kim, et al. 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