FOLR1 encodes folate receptor alpha (FRα), a glycosylphosphatidylinositol-anchored membrane protein that mediates cellular uptake of folate and reduced folic acid derivatives, particularly 5-methyltetrahydrofolate 12. FRα binds folates with high affinity at neutral pH; receptor-mediated endocytosis and acidic pH trigger conformational changes that release folates intracellularly 3. Beyond folate transport, emerging evidence indicates FOLR1 participates in signaling pathways including JAK-STAT3 and ERK1/2, independent of one-carbon metabolism 4. FRα is essential for normal embryonic development and cell proliferation 5. Clinically, FOLR1 is highly overexpressed in multiple cancers, including ovarian, non-small-cell lung, and colon cancers, correlating with increased progression and poor prognosis 6. This expression pattern makes FRα an excellent therapeutic target; mirvetuximab soravtansine, an antibody-drug conjugate targeting FRα, demonstrated superior progression-free survival (5.62 vs. 3.98 months) and overall survival (16.46 vs. 12.75 months) in platinum-resistant ovarian cancer 7. Additionally, FOLR1 dysfunction causes cerebral folate deficiency syndrome; loss-of-function FOLR1 mutations or FRα-directed autoantibodies impair brain folate transport, causing neuropsychiatric disorders 8. Folinic acid, bypassing impaired FRα-mediated transport via alternative pathways, shows therapeutic promise in autism spectrum disorder patients with FRα autoantibodies 5.