The U.S. Food and Drug Administration approved leucovorin (Wellcovorin) for cerebral folate deficiency caused by variants in the folate receptor 1 gene, narrowing the drug’s labeled use to a specific, ultra-rare genetic syndrome. The decision, announced by FDA officials, was made on a review of case reports and mechanistic data rather than new randomized trials. The agency explicitly stopped short of endorsing leucovorin as a treatment for autism spectrum disorder despite high-profile White House statements and a surge in off-label prescribing. The FDA’s action formalizes access for the very small number of patients with confirmed CFD-FOLR1 while rejecting broader indications for autism without robust clinical evidence. Industry and clinical groups warned that the political attention preceding the approval had already driven a spike in prescriptions, raising concerns about supply and off-label use. Regulators and clinicians now face follow-on questions about how to manage increased demand and ensure appropriate testing to identify patients with the specific genetic defect.