Bone morphogenetic proteins (BMPs) bind to two types of membrane receptors. Type II receptor phosphorylates type I receptor, then the phosphorylated type I receptor phosphorylates downstream effectors, such as Smads. Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant disorder characterized by progressive heterotopic ossification in skeletal muscle tissue. ALK2, a BMP type I receptor has been mutated in patients with FOP. The mutant ALK2 phosphorylates Smads in the absence of BMPs. In FOP, muscle injury may enhance BMP signaling via Smads to induce acute heterotopic ossification. Inhibitors of the BMP-Smad pathway will be useful to develop novel treatments for FOP.
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