A heterozygous missense mutation in activin receptor IA/activin-like kinase-2 
(ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor, is responsible 
for fibrodysplasia ossificans progressiva (FOP), the most catastrophic disorder 
of skeletal metamorphosis in humans. The discovery of the FOP gene establishes a 
crucial milestone in understanding FOP, reveals a highly conserved target in the 
BMP signaling pathway for drug development and specifically stimulates 
therapeutic approaches for the development of inhibitors for ACVR1/ALK2 
signaling. Effective therapies for FOP, and possibly for more common conditions 
of heterotopic ossification, will be based on interventions that selectively 
block promiscuous ACVR1/ALK2 signaling, and/or themolecular triggers, responding 
cells and tissue microenvironments that facilitate aberrant skeletal 
metamorphosis in a permissive genetic background of increased BMP pathway 
activity.