Congratulations to Arthur Marivin, Anthony Leyme and colleagues in the Garcia-Marcos lab who have reported a new mechanism of action for disease-associated G protein mutants in their recentScience Signaling publication and highlighted in a Podcast. They found that a rare hereditary disease is caused by G protein mutants that act as dominant negative proteins that block endothelin GPCR signaling during embryo development. This is the first example of a human disease caused by G protein mutants that arises from a dominant negative function.