Mutations found in Noonan syndrome destabilize the autoinhibited form of the enzyme without substantially affecting the intrinsic catalytic activity of the phosphatase domain, leading to increased basal phosphatase activity, elevated scaffolding activity, and downstream induction of ERK (Araki et al., 2004; Niihori et al., 2005). The gene discussed is MAPK1; the disease is Noonan syndrome.