Federal regulators updated the status of leucovorin after high‑profile public statements suggested the drug could broadly benefit children with autism. The FDA approved high‑dose leucovorin for a rare genetic cerebral folate deficiency linked to receptor 1 mutations—an indication affecting fewer than 1 in 1 million people—but rejected broader endorsement for autism without evidence from trials. Separately, the agency issued guidance widening use of leucovorin for the specific genetic deficiency without new randomized trial data, a move that drew scrutiny for relying on limited evidence. The contrasting communications have fueled confusion among clinicians and families and prompted a surge in prescriptions that strained supply chains. Regulatory context: the episode highlights the limits of anecdotal or preliminary claims in regulatory decision‑making and reinforces the FDA’s requirement for robust evidence when expanding indications beyond narrowly defined genetic disorders.