Interestingly, recently published data suggest that dephosphorylation of RAF S259 is the primary pathogenic mechanism in the activation of several RAF1 mutants identified in patients with Noonan syndrome [36], which emphasizes the role of the PP1C holoenzyme complex and Shoc2, particularly, in the regulation of ERK1/2 pathway. This evidence concerns the gene SHOC2 and Noonan syndrome.