This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-NH group of donors with NAD+ or NADP+ as acceptor.

This enzyme participates in glyoxylate and dicarboxylate metabolism and one carbon pool by folate.

As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes 1A4I, 1DIA, 1DIB, 1DIG, 1LU9, 1LUA, 2C2X, and 2C2Y.

Mutations of the MTHFD1 gene may disrupt the activity of the enzyme and cause methylenetetrahydrofolate dehydrogenase 1 deficiency, also known as combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia (CIMAH).

The systematic name of this enzyme class is 5,10-methylenetetrahydrofolate:NADP+ oxidoreductase.