Monocarboxylate transporter 4 (MCT4) belongs to a group of membrane proteins responsible for mediating the transfer of various short chain monocarboxylates including lactate, pyruvate, and ketones across the cell membrane. MCTs also transfer H⁺ resulting in acidification of the tissue microenvironment, thus playing an important role in the control of intracellular pH by proton‐coupled release. MCT4 transports monocarboxylates in a ratio of 1:1 with H⁺.

Transport activity of MCT4 is enhanced by carbonic anhydrase II, which has been suggested to function as a “proton antenna” for MCT4^1-3.

The SLC16 gene family of MCTs comprises 14 members with a structure that contains 12 transmembrane domains. Among MCT members, only MCT1 and MCT4 catalyze the proton-coupled transport of lactate and H⁺. The distribution of MCTs is different by cell type. MCT4 is highly expressed in glycolytic cells, such as skeletal muscle fibers, astrocytes, leukocytes, chondrocytes, and some mammalian cell lineages.

MCT4 is extensively investigated in cancer cells and is considered to be a metabolic target for anticancer therapies^2-4.