{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRFTN1, also known as Raftlin, is a lipid raft–associated protein that plays a critical role in the organization and function of membrane microdomains essential for immune receptor signaling. In B lymphocytes, Raftlin is targeted to lipid rafts via fatty acylation of its N‐terminal residues, where it facilitates the assembly and maintenance of these platforms and thereby modulates B-cell receptor (BCR)–mediated tyrosine phosphorylation and calcium mobilization events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, Raftlin is required for the cellular uptake of extracellular double-stranded RNA analogs such as poly(I:C): it translocates from the cytoplasm to the plasma membrane where it colocalizes with poly(I:C) and later directs the ligand to TLR3-positive endosomes to trigger type I interferon production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, Raftlin modulates clathrin-mediated internalization of TLR4 in response to lipopolysaccharide, selectively enhancing TICAM-1–dependent interferon-β signaling while leaving NF-κB activation largely unaffected."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nClinical and pathological studies have further implicated RFTN1 in human disease. Genetic investigations have demonstrated an association between sequence variations in RFTN1 and glaucoma-related optic disc parameters, suggesting a role in ocular tissue biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the context of oncogenesis, RFTN1 is overexpressed in primary gastric cancer tissues where it contributes to enhanced cell proliferation, G0/G1-to-S phase transition, and resistance to apoptosis via modulation of the AKT and p38 signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Elevated Raftlin levels have also been observed in chronic inflammatory conditions: in patients with chronic rhinosinusitis with nasal polyps (especially smokers), increased expression in the nasal epithelium correlates with higher interleukin-17 and tumor necrosis factor-α levels, implying involvement in epithelial remodeling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Furthermore, increased Raftlin expression has been linked with markers of oxidative stress in vertebral endplates of patients with low back pain"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and alterations in inflammatory biomarkers in periodontal disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings underscore the multifaceted functions of RFTN1 in both immune signaling and disease pathogenesis. By orchestrating lipid raft integrity and governing receptor endocytosis, Raftlin not only modulates critical immune responses but also impacts cell proliferation and inflammatory processes. Its diverse roles in mediating B-cell activation, toll-like receptor signaling, and cellular homeostasis highlight its potential as a promising biomarker and therapeutic target across a range of pathological conditions.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kazuko Saeki, Yoshiki Miura, Daisuke Aki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The B cell-specific major raft protein, Raftlin, is necessary for the integrity of lipid raft and BCR signal transduction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/emboj/cdg293"}], "href": "https://doi.org/10.1093/emboj/cdg293"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12805216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12805216"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ayako Watanabe, Megumi Tatematsu, Kazuko Saeki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Raftlin is involved in the nucleocapture complex to induce poly(I:C)-mediated TLR3 activation."}]}, {"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.M110.185793"}], "href": "https://doi.org/10.1074/jbc.M110.185793"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21266579"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21266579"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Megumi Tatematsu, Ryuji Yoshida, Yuka Morioka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Raftlin Controls Lipopolysaccharide-Induced TLR4 Internalization and TICAM-1 Signaling in a Cell Type-Specific Manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1501734"}], "href": "https://doi.org/10.4049/jimmunol.1501734"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27022195"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27022195"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jian-Huan Chen, Degui Wang, Chukai Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interactive effects of ATOH7 and RFTN1 in association with adult-onset primary open-angle glaucoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Invest Ophthalmol Vis Sci (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1167/iovs.11-8277"}], "href": "https://doi.org/10.1167/iovs.11-8277"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22222511"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22222511"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chaowei Deng, Lu Zhang, Xiaoping Ma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RFTN1 facilitates gastric cancer progression by modulating AKT/p38 signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Res Pract (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.prp.2022.153902"}], "href": "https://doi.org/10.1016/j.prp.2022.153902"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35490655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35490655"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yu-Tsai Lin, Ming-Hsien Tsai, Yan-Ye Su, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression of Major Lipid Raft Protein Raftlin in Chronic Rhinosinusitis with Nasal Polyps in Smoking and Non-Smoking Patients Correlated with Interleukin-17 and Tumor Necrosis Factor-α Levels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomolecules (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/biom12091316"}], "href": "https://doi.org/10.3390/biom12091316"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36139155"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36139155"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "İlter Demirhan, Erkan Oner, Zafer Yuksel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Raftlin and 8-iso-prostaglandin F2α levels and gene network analysis in patients with Modic changes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Spine J (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00586-023-07757-7"}], "href": "https://doi.org/10.1007/s00586-023-07757-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37208489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37208489"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Eda Çetin Özdemir, Meral Uzunkaya, Hasan Gündoğar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between raftlin and presepsin levels with periodontal healthy and disease conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Oral Biol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.archoralbio.2024.105880"}], "href": "https://doi.org/10.1016/j.archoralbio.2024.105880"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38278125"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38278125"}]}]}]}