Reduced folate carrier (RFC) and Folate receptor (FR) transport systems (RFC/FR)

The folate transport system, primarily comprising the Reduced Folate Carrier (RFC/SLC19A1) and Folate Receptors (FRs), is the principal mechanism for cellular folate uptake, which is vital for DNA synthesis, repair, and methylation (Matherly & Hou, 2008, Vitam Horm). RFC is a ubiquitously expressed, high-capacity bidirectional anion exchanger that serves as the primary entry point for reduced folates and antifolate chemotherapeutics like methotrexate in systemic tissues (Zhao & Goldman, 2007, Curr Opin Clin Nutr Metab Care). In contrast, Folate Receptors, particularly the alpha isoform (FRα), are high-affinity binding proteins that internalize folates via receptor-mediated endocytosis and exhibit restricted expression in normal tissues but are highly overexpressed in various epithelial malignancies (Cheung et al., 2016, Oncotarget). This differential expression pattern makes FRα an attractive target for highly specific therapies, such as antibody-drug conjugates like mirvetuximab soravtansine, which deliver cytotoxic payloads directly to tumor cells (FDA, 2022, Elahere Label). Conversely, the RFC is often a site of resistance in cancer treatment, as its downregulation or mutation can limit the intracellular accumulation of antifolates. Together, these transport systems maintain folate homeostasis and are critical determinants of the efficacy and toxicity of folate-based therapies in oncology and inflammatory diseases.

Other names

SLC19A1FOLR1Reduced folate carrier 1Folate receptor alphaFolate binding proteinFBPSolute carrier family 19 member 1Folate receptor 1RFC1

Facilitates the cellular uptake of natural folates and antifolate drugs via anion exchange (RFC) or receptor-mediated endocytosis (FRs), thereby supporting or inhibiting nucleotide biosynthesis.