ACVR1 and fibrodysplasia ossificans progressiva: However, given that one of the most debilitating aspects of FOP is the cumulative heterotopic bone and its associated comorbidities, the fact that Activin A directly acts on mutant ACVR1 to trigger HO in FOP indicates that this is an obligatory pathophysiologic mechanism, and moreover one with implications for the development of therapeutics.