Fibrodysplasia ossificans progressiva (FOP) is a disabling genetic condition 
that leads to the formation of a second (heterotopic) skeleton, and is the most 
catastrophic disorder of heterotopic ossification in humans. Throughout 
childhood and early adult life, FOP progressively immobilizes all of the joints 
of the normotopic skeleton, rendering movement impossible. At present, there is 
no effective prevention or treatment. Recently, a recurrent mutation in the 
glycine-serine activation domain of the activin receptor IA/activin-like 
kinase-2, a bone morphogenetic protein type I receptor, was reported in all 
sporadic and familial cases of classic FOP, making this one of the most highly 
specific disease-causing mutations in the human genome. The discovery of the FOP 
gene establishes a critical milestone in understanding FOP, reveals a highly 
conserved druggable target in the TGF-beta/bone morphogenetic protein signaling 
pathway and compels therapeutic approaches for the development of small molecule 
signal transduction inhibitors for activin-like kinase-2. Effective therapies 
for FOP, and possibly for a vast array of more common conditions of heterotopic 
ossification, will be based on blocking activin-like kinase-2, a critical node 
in the BMP signaling pathway.