Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX). (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin + 2 NADP(+) = 2 H(+) + L-erythro-biopterin + 2 NADPH Cofactor biosynthesis; tetrahydrobiopterin biosynthesis; tetrahydrobiopterin from biopterin: step 1/1. Homotetramer. Belongs to the short-chain dehydrogenases/reductases (SDR) family.