SPRED1 and neurofibromatosis type 1: To gain structural insight into how neurofibromin interacts with SPRED1 without affecting KRAS inactivation and to understand the structural basis of pathogenic SPRED1 and NF1 mutations in Legius syndrome and neurofibromatosis type 1, we attempted to solve the structure of the ternary complex composed of NF1(GRD), SPRED1(EVH1), and GMPPNP-bound KRAS (Figure 1A).