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Folate receptor alpha (FRα) is a membrane-bound protein that facilitates high-affinity folate transport, essential for cell metabolism, DNA synthesis, and repair, particularly in rapidly dividing cancer cells with increased folate demands. This receptor, encoded by the FOLR1 gene, employs a potocytosis mechanism that leads to both membranous and cytoplasmic localization and is selectively overexpressed in certain epithelial malignancies while remaining highly restricted in normal tissues. FRα expression correlates with tumor stage and grade, suggesting a role in tumor progression by enhancing folate uptake or generating regulatory signals. Its regulation is influenced by extracellular folate levels, homocysteine accumulation, hormones, transcription factors, and genetic mutations. Members of the folate receptor family share highly conserved sequences in the open reading frames but differ in amino acids in the 5′ untranslated regions and as a consequence can differ in function and tissue expression. Given the selective overexpression of FRα in tumors and its association with aggressive cancer phenotypes, FRα is a valuable marker for studying tumor biology and progression, particularly in epithelial cancers.
