Our results not only are concur with the description of a Shoc2 mutant involved in a Noonan-like syndrome by deregulated ERK activation [15], but also with inhibition of the Ras-ERK pathway by Erbin, another protein rich in leucine domains that blocks Shoc2 interaction with Raf and Ras, thus down-regulating ERK activation through molecular binding between Erbin and Shoc2 [37], [38] that is enhanced by Desmoglein-1 [39]. This evidence concerns the gene RAF1 and Noonan syndrome.