Fibrodysplasia ossificans progressiva (FOP) is a rare, incapacitating syndrome characterized by acute inflammation that precedes extraskeletal ossification of connective tissues such as skeletal muscles, ligaments and tendons. Furthermore, bridges of bone form and fuse skeletal joints, progressively restricting movement.  In classic FOP, this heterotopic ossification is engineered by a heterozygous mutation (617G>A) in the Activin (A) receptor type I (ACVR1) which produces  the (R206H) mutation in the protein Activin-like kinase 2 (ALK2). ALK2 is a type I serine/threonine kinase bone morphogenic protein (BMP) receptor. BMP signaling is a highly conserved pathway in vertebrate anatomy that tightly regulates cellular differentiation in the development of cardiac, CNS, cartilage and bone tissues. In FOP, activity of the BMP pathway is greatly upregulated due to a gain of function of mutated ALK2.  Even without BMP binding to the extracellular domain, ALK2 will phosphorylate downstream targets, instructing the body to grow bone. It is the phosphorylation of ALK2’s intracellular glycine/serine rich domain which flips this molecular switch on. Stopping this phosphorylation mechanism is just one possible therapeutic target for FOP. Other promising research lies in the development of allele-specific RNA interference (ASP-RNAi) to selectively target mutated ALK2 for degradation. Still further explorations attempt to prevent heterotopic ossification by altering skeletal progenitor cells via retinoids. Hopefully, with continued investigations into FOP, restoration of this perturbed signaling pathway looms in the near future.