MTHFS, also known as 5-formyltetrahydrofolate cyclo-ligase, is a cytosolic protein involved in the formate metabolic process. MTHFS, with a magnesium cofactor, catalyzes the ATP-dependent reaction that reduces 5-formyltetrahydrofolate (5-MTHF) to 5,10-methenyltetrahydrofolate(MTHF). MTHF is the substrate used by MTHFR (methylenetetrahydrofolate reductase) to generate 5-MTHF.