{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC7A8 encodes LAT2, a sodium‐independent transporter that mediates the cellular uptake of neutral amino acids—such as glutamine and leucine—that are critical for energy metabolism and cell signaling pathways including mTOR activation. In addition to transporting key metabolic substrates, LAT2 facilitates the uptake of bioactive molecules like L‐CSNO, thereby influencing nitric oxide signaling and related physiological responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nLAT2 plays diverse roles in normal physiology. In the placenta, it contributes to materno–foetal transfer of essential amino acids, with studies showing that its activity and subcellular localization can be modulated by conditions such as maternal overweight."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the developing brain, alterations in LAT2 mRNA levels have been observed during neurodifferentiation, suggesting a potential impact on early cortical development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In the inner ear, loss‐of‐function mutations in SLC7A8 have been linked to age‐related hearing loss"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", while interaction studies in intestinal epithelia reveal that LAT2, in complex with CD98, can be modulated by cell adhesion molecules such as ICAM‐1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinically, aberrant expression or mutation of SLC7A8 is emerging as a significant factor in various pathologies. Overexpression of LAT2 has been associated with chemoresistance in pancreatic cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ", while alterations in its function have been implicated in multi‐drug resistance in esophageal squamous cell carcinoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, SLC7A8 overexpression correlates with tumor progression in lung adenocarcinoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and has been noted in estrogen receptor–positive breast cancer, suggesting a role in prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Its involvement in the transport of chemotherapeutic agents such as melphalan"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "and regulation by progesterone in uterine leiomyoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "further highlight the clinical relevance of this transporter. Recent structural and functional studies on the 4F2hc–LAT2 heterodimer provide insights into its molecular mechanism and the impact of disease‐associated mutations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": " Additionally, emerging genetic associations extend the clinical spectrum of SLC7A8 to include osteosarcoma"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "and possibly contribute to altered L‐DOPA uptake relevant to hypertensive chronic kidney disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mengyu Feng, Guangbing Xiong, Zhe Cao, et al. 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