SLC2A8 (GLUT8) is an insulin-regulated facilitative hexose transporter mediating glucose and fructose transport across cell membranes. In hepatocytes, SLC2A8 facilitates dietary trehalose uptake, which triggers a starvation signal through AMPK and ULK1 activation, promoting hepatic autophagy 1. Trehalose accumulation in the endolysosomal system causes mild lysosomal pH elevation, activating TFEB (transcription factor EB) and the autophagy-lysosomal biogenesis response 2. In motoneuron models, trehalose-mediated SLC2A8 activity ameliorates neurodegeneration by inducing TFEB-dependent autophagy and clearance of misfolded proteins 3. SLC2A8 also transports dehydroascorbate and supports cellular respiration in trophoblasts 4. In reproductive tissues, SLC2A8 is essential for spermatozoal ATP production and motility 5 and oocyte metabolism 6. Disease relevance includes neurodegenerative diseases and early Alzheimer's disease, where SLC2A8 upregulation correlates with faster cognitive decline 7. Hepatic SLC2A8 is downregulated by ANGPTL3 during metabolic dysfunction-associated steatotic liver disease 8. SLC2A8 knockout mice exhibit increased locomotor activity and reduced risk assessment behavior 9, suggesting a role in neuronal glucose metabolism and behavior regulation.