SLC2A5 encodes GLUT5, a fructose transporter with high specificity for fructose uptake and only low activity with other monosaccharides 1. GLUT5 mediates cellular fructose uptake with low efficiency for 2-deoxyglucose 2. The protein functions across multiple physiological contexts: it is essential for intestinal fructose absorption and regulates salt uptake and blood pressure in response to dietary fructose intake. Mechanistically, SLC2A5 expression is regulated by SNAI1/SNAI2 transcription factors, which can be induced by histone deacetylase inhibitors 3. High fructose exposure drives SLC2A5-dependent uptake and catabolism to fructose 6-phosphate, metabolically rewiring cells toward altered functional states 4. In endothelial cells, SLC2A5-mediated fructose metabolism activates AMPK signaling and mitochondrial respiration to promote angiogenesis 5. Clinical relevance: SLC2A5 overexpression promotes tumor progression through fructose-driven metabolic reprogramming and immune evasion 6. Early-life high fructose exposure impairs microglial phagocytosis and neurodevelopment via GLUT5-dependent mechanisms, with GLUT5 deletion rescuing anxiety-like behavior 4. SLC2A5 is implicated in critical COVID-19 severity and acute respiratory distress syndrome pathogenesis 78. Additionally, SLC2A5 may represent a therapeutic target in Alzheimer's disease, where microglial fructose metabolism dysregulation contributes to neuroinflammation 9.