Reduced folate carrier protein (RFC)

The **reduced folate carrier protein** (RFC, also known as SLC19A1) is a transmembrane transporter and member of the major facilitator superfamily that is the primary route for folate and antifolate drug entry into mammalian cells[2][5][7][9]. It functions via anion exchange, importing folates (vitamin B9 derivatives)—essential cofactors for one-carbon transfer reactions necessary for nucleic acid and amino acid synthesis—into the cell[5][9][10]. RFC is also the main pathway for cellular uptake of classical antifolate chemotherapeutics, such as methotrexate, and thus is a critical determinant of chemotherapy response and resistance in cancer therapy[5][7][9]. RFC is widely expressed in human tissues; mutations or altered levels of RFC can result in disease states like drug resistance, hereditary folate malabsorption, and megaloblastic anemia[7][9]. The human RFC protein has 12 transmembrane domains, with functionally critical residues involved in substrate recognition and transport[1][5][9].

Other names

Reduced folate carrierRFCRFC1solute carrier family 19 member 1SLC19A1

Facilitates uptake of folate and antifolate drugs into cells by anion exchange across the plasma membrane Determines cellular sensitivity to antifolate chemotherapy (drug transport-dependent cytotoxicity)