DNA methylation also mediates overexpression of glucose transporter 1 (GLUT1) by epigenetic loss of Derlin-3, a key gene involved in the proteasomal degradation of GLUT1.124 Conversely, promoter hypomethylation contributes to upregulation of pyruvate kinase ioszyme 2 (PKM2) in multiple cancer types.125 PKM2 is a less active isomer that drives glucose flux towards macromolecules biosynthesis and is the predominant isoform in actively proliferating cells. The gene discussed is PKM; the disease is cancer.