The activation of serine biosynthesis pathway enhances NADPH generation in cancer cells.63 Conversely, eliminating serine from the medium decreases the NADPH/NADP+ ratio and impairs cancer cell growth.64 Methylene tetrahydrofolate dehydrogenases (MTHFD1 in cytosol and MTHFD2 or MTHFD2L in mitochondria) catalyze the oxidation of 5,10-methylene-THF (CH2-THF) to form 10-formyl-THF, and 10-formyl-THF dehydrogenases (ALDH1L1 in cytosol and ALDH1L2 in mitochondria) catalyze the oxidization of 10-formyl-THF to generate CO2 with concomitant NADPH production. This evidence concerns the gene MTHFD2L and cancer.