FRalpha

FRalpha, or folate receptor alpha, is a high-affinity receptor for folate (vitamin B9) and reduced folates. It is a member of the folate receptor family and is encoded by the FOLR1 gene. FRα is a glycosylphosphatidylinositol (GPI)-anchored cell-surface protein with a short cytoplasmic tail and lacks a transmembrane domain, placing it on the outer leaflet of the plasma membrane.

In normal tissues, FRα shows restricted expression, predominantly in the placenta, choroid plexus, and proximal tubules of the kidney; expression in most adult tissues is low. The receptor is of interest because many cancers, especially epithelial ovarian cancer, can overexpress FRα, with variable expression in breast, lung, and kidney cancers. This overexpression makes FRα an attractive target for diagnostic and therapeutic strategies.

FRα binds folate with high affinity and mediates cellular uptake by receptor-mediated endocytosis. After endocytosis, folate is released in endosomes and transported to the cytosol, and the receptor is recycled back to the cell surface to continue uptake.

Clinical relevance arises from the differential expression of FRα in tumors versus normal tissues. Therapeutic approaches include folate-conjugated drugs and folate receptor-targeted antibodies or antibody-drug conjugates, as well as imaging agents for PET or SPECT that visualize FRα-positive tumors. Diagnostic methods such as immunohistochemistry or mRNA analysis are used to assess FRα expression and inform patient selection for FRα-targeted therapies.

FRalpha is one of several folate receptor isoforms; the gene FOLR1 encodes FRα.