An alternative mechanism proposed by Koivunen et al. (2012) suggests that d-2HG acts as a cofactor to promote the hydroxylase activity of the Eg1N prolyl-4-hydroxylase and subsequent downregulation of HIF1α, contributing to the pathogenesis of IDH mutant gliomas (Koivunen et al., 2012). Here, IDH2 is linked to glioma.