{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC7A7 encodes the y⁺LAT1 protein, the catalytic light chain of the heterodimeric amino acid transporter complex known as system y⁺L. This transporter is predominantly expressed at the basolateral membrane of epithelial cells in the kidney and intestine, where it facilitates the bidirectional exchange of cationic amino acids—such as arginine, lysine, and ornithine—with neutral amino acids. Defective function of y⁺LAT1 due to a broad spectrum of SLC7A7 mutations is the molecular basis of lysinuric protein intolerance (LPI), a recessively inherited disorder characterized by aminoaciduria, protein intolerance, and multisystem involvement. In addition, studies have demonstrated that mutant forms of y⁺LAT1 may exhibit abnormal subcellular trafficking and impaired heterodimerization with the 4F2hc partner, while transcriptional regulatory mechanisms (including alternative promoter usage) underlie tissue‐specific expression patterns critical for maintaining physiological amino acid homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its well‐established role in epithelial transport, SLC7A7 function is critical in immune regulation. During the differentiation of monocytes into macrophages, there is a marked induction of SLC7A7 expression and an increase in the activity of system y⁺L, which appears to be instrumental in modulating arginine flux. This regulation not only impacts intracellular arginine and lysine levels but also influences macrophage activation and inflammatory responses. Experimental silencing of SLC7A7 in macrophagic and airway epithelial cells leads to an aberrant increase in pro‐inflammatory mediators via NFκB activation, suggesting that under physiological conditions, y⁺LAT1 activity acts as a braking mechanism to restrain inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its classic involvement in LPI and immune cell function, altered SLC7A7 expression is emerging as a factor in other pathological contexts. Overexpression of SLC7A7 has been observed in glioblastoma, where it correlates with increased tumor proliferation and portends a poor prognosis. Moreover, common polymorphisms in SLC7A7 have been linked to an elevated risk of glioma, further highlighting the significance of its regulated amino acid transport in cellular metabolic networks. There is even evidence suggesting that disturbances in this transporter’s activity may contribute to impaired transplacental nutrient exchange in gestational disorders, underscoring the broader physiological importance of SLC7A7."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maria Pia Sperandeo, Generoso Andria, Gianfranco Sebastio "}, {"type": "b", "children": [{"type": "t", "text": "Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20589"}], "href": "https://doi.org/10.1002/humu.20589"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17764084"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17764084"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Maria P Sperandeo, Simona Paladino, Luigi Maiuri, et al. 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