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Beyond physiological necessity, GLUT1 dysregulation drives a broad pathological spectrum. While genetic haploinsufficiency precipitates severe neurological energy crises like Glut1 deficiency syndrome (Glut1DS), oncogenic networks hyperactivate GLUT1 as the central executor of the Warburg effect to fuel malignant proliferation. Despite its immense therapeutic potential, severe on\u2010target toxicity in normal tissues and adaptive metabolic plasticity remain critical roadblocks to systemic GLUT1 inhibition. This review comprehensively synthesizes GLUT1's multidimensional regulatory networks in health and disease, dissecting how its overexpression fundamentally remodels the tumor microenvironment (TME). We elucidate how GLUT1\u2010driven \u201cmetabolic competition\u201d fosters metabolic immune exclusion and drives therapeutic resistance. Furthermore, we map the paradigm shift from traditional systemic blockades to emerging precision interventions. Specifically, we highlight \u201cTrojan horse\u201d glycan\u2010functionalized nanocarriers, targeted protein degradation technologies like PROTACs, and metabolically engineered CAR\u2010T cells. By conceptualizing GLUT1 as the linchpin of the immunosuppressive ecosystem, this work provides a strategic roadmap for precision metabolic immuno\u2010oncology, guiding the development of novel therapies that maximize durable efficacy while minimizing collateral physiological damage.<\/jats:p>","DOI":"10.1002\/mco2.70874","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:53:13Z","timestamp":1784789593000},"source":"Crossref","is-referenced-by-count":0,"title":["Glucose Transporter 1 in Health and Disease"],"prefix":"10.1002","volume":"7","author":[{"given":"Yi","family":"Tai","sequence":"first","affiliation":[{"name":"Department of Colorectal Surgery Zhejiang Cancer Hospital  Hangzhou China"},{"name":"Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Musculoskeletal Oncology State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine Guangdong Provincial Clinical Research Center for Cancer Sun Yat\u2010sen University Cancer Center  Guangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery Zhejiang Cancer Hospital  Hangzhou China"},{"name":"Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7227-3671","authenticated-orcid":false,"given":"Weidong","family":"Han","sequence":"additional","affiliation":[{"name":"Hangzhou Institute of Medicine (HIM) Chinese Academy of Sciences  Hangzhou China"},{"name":"Department of Colorectal Medical Oncology Zhejiang Cancer Hospital  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00055.2009"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1159\/000104457"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201900544"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e29655"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.vh.2024.06.001"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16142363"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom7010016"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/15216540701313788"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03174092"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nu.16.070196.001315"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2024.08.008"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.119.316463"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adp4120"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-023-08535-w"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.70044"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2023-0456OC"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202304617"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.04.022"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.08.016"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2021.09.002"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1037341"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-0172-2"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-21-1059"},{"issue":"1","key":"e_1_2_15_25_1","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1186\/s13046-023-02927-3","article-title":"AMPK\u2010HIF\u20101\u03b1 Signaling Enhances Glucose\u2010Derived De Novo Serine Biosynthesis to Promote Glioblastoma Growth","volume":"42","author":"Yun H. 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