Solute carrier family 19 member 1 (SLC19A1)

Solute carrier family 19 member 1 (SLC19A1), commonly known as the Reduced Folate Carrier (RFC), is the primary protein responsible for the transport of reduced folates from the extracellular environment into the cytoplasm. It functions as an organic anion antiporter, exchanging intracellular organic phosphates for extracellular folates, and is ubiquitously expressed in mammalian tissues to maintain one-carbon metabolism (UniProt P41440). In addition to its role in nutrient uptake, SLC19A1 is the major gateway for several clinically important antifolate chemotherapeutics, including methotrexate and pemetrexed (PubMed: 24552113). Recent research has also identified SLC19A1 as a key transporter for cyclic dinucleotides like cGAMP, which are critical for activating the STING-mediated innate immune response (PubMed: 31511694). Alterations in SLC19A1 expression or function are frequently associated with methotrexate resistance in cancer treatment and have been linked to developmental defects such as neural tube defects due to impaired folate transport during embryogenesis (PubMed: 11844478).

Other names

Reduced folate carrier 1RFC1Folate transporter 1Intestinal folate carrier 1IFC-1Placental folate transporter

Acts as a bidirectional facilitative transporter that mediates the uptake of reduced folates and antifolate drugs into cells via an organic anion exchange mechanism.