Reduced folate carrier 1 (RFC1 (SLC19A1))

Reduced folate carrier 1 (SLC19A1) is a membrane transporter primarily responsible for the high-affinity, carrier-mediated influx of reduced folates and antifolate drugs such as methotrexate into mammalian cells, including hepatocytes. It distinguishes itself from other folate transporters (such as the proton-coupled folate transporter, PCFT) by its substrate specificity and physiological pH optimum. OATPs (notably OATP1B1 and OATP1B3) also mediate hepatic uptake of methotrexate, impacting systemic disposition, efficacy, and toxicity of methotrexate-based therapies. The coordinated action and expression of these influx transporters in the liver critically influence methotrexate pharmacokinetics and patient response, and they are relevant in the context of both therapeutic benefit and drug safety[1][2][3][4][7].

Other names

SLC19A1Reduced folate carrierRFCOATP1B1 (SLCO1B1)OATP1B3 (SLCO1B3)

Carrier-mediated influx of methotrexate and folates into hepatocytes (and other cells); methotrexate entry enables inhibition of nucleotide synthesis enzymes[1][2][4][6][7]