Folate Receptor alpha (FR-alpha)

Folate receptor alpha (FR-alpha, FOLR1) is one of three human folate receptors and the principal high-affinity transporter for reduced folates in epithelial tissues. N-linked glycans govern its membrane trafficking, and the receptor constitutively cycles between the cell surface and acidic endosomes, releasing bound folate as luminal pH falls. Biallelic FOLR1 loss of function causes cerebral folate transport deficiency, a treatable neurodevelopmental disorder. In oncology, strong FR-alpha expression in epithelial ovarian, fallopian tube, and non-squamous non-small cell lung cancers underpins antibody-drug conjugates, folate-drug conjugates, PET imaging agents, and CAR-T programs. The receptor localizes to the apical surface of polarized epithelial cells.