Folate receptor beta and other folate transporters (FOLR2/SLC19A1/SLC46A1)

Folate receptor beta (FOLR2) and other folate transporters, such as the reduced folate carrier (SLC19A1) and proton-coupled folate transporter (SLC46A1), are essential proteins that mediate the cellular uptake of folates required for DNA synthesis and one-carbon metabolism (1.1.1, 1.3.1). While SLC19A1 is ubiquitously expressed for general folate homeostasis, FOLR2 is specifically upregulated on myeloid-lineage cells, particularly M2-polarized tumor-associated macrophages (TAMs) and synovial macrophages in inflammatory diseases like rheumatoid arthritis (1.1.3, 1.4.1). This restricted expression pattern makes FOLR2 a high-value target for selective drug delivery using folate-drug conjugates and for diagnostic imaging of active inflammation (1.5.1, 1.5.2). In oncology, these transporters are critical for the efficacy of antifolate chemotherapies like methotrexate and pemetrexed, which rely on them for entry into malignant cells (1.3.2). Therapeutic strategies currently under investigation include FOLR2-targeted CAR-T cells and immunomodulators designed to reprogram the immunosuppressive tumor microenvironment (1.2.2, 1.5.3). Understanding the interplay between these various transporters is vital for optimizing targeted therapies and overcoming mechanisms of drug resistance in both cancer and chronic inflammatory conditions (1.5.4).

Other names

Folate receptor betaFOLR2FR-betaReduced folate carrierSLC19A1RFCProton-coupled folate transporterSLC46A1PCFTFolate receptor alphaFOLR1Folate receptor 2Folate-binding protein

Facilitation of cellular folate and antifolate uptake via receptor-mediated endocytosis (FOLR1/2) or facilitative/proton-coupled transmembrane transport (SLC19A1/SLC46A1).