SLC5A8 (SMCT1) is a sodium-dependent monocarboxylate transporter that mediates electrogenic cotransport of short-chain fatty acids, ketone bodies, and other monocarboxylates across epithelial membranes 1. The transporter operates with a Na+:substrate stoichiometry of 2:1 to 4:1 and exhibits chloride-dependent activity, transporting substrates including butyrate, lactate, pyruvate, and beta-hydroxybutyrate 1. In the intestinal epithelium, SLC5A8 mediates apical membrane uptake of short-chain fatty acids and monocarboxylate drugs, with butyrate serving as a key physiological substrate 2. In neurons, SLC5A8 likely contributes to lactate and ketone body entry, supporting neuronal energy metabolism and function 3. Notably, SLC5A8 functions as a tumor suppressor, with gene silencing via CpG island hypermethylation occurring in colon, cervical, prostate, and brain cancers 4. SLC5A8 overexpression suppresses cancer cell proliferation and migration, arresting cells in G1/S phase and reducing tumor growth in xenograft models 5. Transcriptional regulation involves C/EBPbeta and Sp1 transcription factors 6. GHB (gamma-hydroxybutyrate) is also transported by SLC5A8, with therapeutic implications for narcolepsy and abuse disorders 7.