Considering the phenotypic similarity between Legius syndrome and neurofibromatosis type 1, as well as the observation that NF1 is recruited to the plasma membrane by SPRED1, it has been hypothesized that mutations in SPRED1(EVH1) could cause Legius syndrome due to an inability to form the NF1-SPRED1 complex (Stowe et al., 2012). Here, SPRED1 is linked to neurofibromatosis type 1.