SLC5A3 is an electrogenic sodium-coupled myo-inositol transporter located on chromosome 21 that plays critical roles in cellular osmoregulation and cancer progression 1. The gene consists of two exons spanning approximately 26 kb, with the entire 2157-bp open reading frame contained in exon 2 2. SLC5A3 actively transports myo-inositol across plasma membranes with a 2:1 Na+:sugar coupling ratio, maintaining cellular myo-inositol gradients essential for osmotic stress response 3. The transporter demonstrates significant clinical relevance in multiple cancers. In acute myeloid leukemia, SLC5A3 represents a metabolic vulnerability for cells dependent on exogenous myo-inositol 4. In pancreatic cancer, SLC5A3 upregulation promotes gemcitabine resistance by stabilizing mitochondrial function and inhibiting apoptosis, while its depletion disrupts mitochondrial dynamics and enhances chemotherapy efficacy 5. Similarly, SLC5A3 promotes growth in non-small cell lung cancer and cervical cancer through myo-inositol-dependent Akt-mTOR pathway activation 67. In glioblastoma, SLC5A3 localizes to migrating cell edges and enhances cell migration 8. Given its chr21 location, SLC5A3 overexpression may contribute to Down syndrome pathophysiology 1.