MTHFD2 and cancer: Studies of MTHFD2L isolated from rat liver mitochondria show that the enzyme behaves as a tightly associated peripheral membrane protein, which is located on the matrix side of the inner mitochondrial membrane.[19] In contrast to MTHFD2, MTHFD2L is not upregulated in cancer,[46] nor does it show an association with growth factor stimulation.[34, 36, 47] Importantly, MTHFD2L does not display a compensatory increase in expression when MTHFD2 is inhibited[46] making it unlikely that the isozyme would be involved in the development of chemoresistance to such inhibitors.