Underscoring the importance of the ERK pathway in development, all RASopathies, which are pathologies due to mutations in the RAS-MAPK pathway, are confined to only gain-of-function mutational defects that lead to inefficient inhibition of the pathway, while there is no documented RASopathy caused by mutational pathway knockout [9]; since such mutations should be more common than gain-of-function mutations, their absence signifies that when they occur, are most likely non-viable. Here, MAPK1 is linked to RASopathy.