Solute carrier family 2, facilitated glucose transporter member 1 (GLUT1) (GLUT1)

Solute carrier family 2, facilitated glucose transporter member 1, commonly referred to as the hexose transport protein or GLUT1, is a transmembrane uniporter responsible for the facilitative movement of glucose across plasma membranes down its concentration gradient. It is highly expressed in erythrocytes and at the blood-brain barrier, ensuring a constant supply of glucose to the central nervous system and other high-demand tissues. In many malignancies, GLUT1 is markedly upregulated as part of the Warburg effect to sustain the high glycolytic flux required for rapid tumor proliferation and survival under hypoxic conditions. Due to its critical role in cancer metabolism, GLUT1 is a focal point for the development of small-molecule inhibitors aimed at starving tumor cells of their primary energy source. However, the essential nature of GLUT1 in brain energy metabolism presents a significant therapeutic challenge regarding selectivity and neurotoxicity. Beyond oncology, mutations in the SLC2A1 gene lead to GLUT1 deficiency syndrome (De Vivo disease), a condition characterized by seizures and developmental delay which is primarily managed through ketogenic diets to provide the brain with alternative metabolic fuels.

Other names

Hexose transport proteinGlucose transporter 1GLUT-1SLC2A1Erythrocyte/brain-type glucose transporterHepG2 glucose transporter

Small-molecule inhibitors typically bind to the transporter in either its inward-facing or outward-facing conformation, competitively or non-competitively blocking the binding site and preventing the translocation of hexose sugars across the cell membrane.