Glucose Transporter 1 in Health and Disease

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Abstract
Glucose Transporter 1 (GLUT1) is the quintessential facilitator of basal glucose uptake, indispensable for maintaining cellular energy homeostasis, particularly across the blood–brain barrier. 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‐target 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‐driven “metabolic competition” 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 “Trojan horse” glycan‐functionalized nanocarriers, targeted protein degradation technologies like PROTACs, and metabolically engineered CAR‐T cells. By conceptualizing GLUT1 as the linchpin of the immunosuppressive ecosystem, this work provides a strategic roadmap for precision metabolic immuno‐oncology, guiding the development of novel therapies that maximize durable efficacy while minimizing collateral physiological damage.
Funding Information
  • National Natural Science Foundation of China (82472739)
  • National Natural Science Foundation of China (82173030)
  • Zhejiang Cancer Hospital (BH2025055)

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