CLN5 and fibrodysplasia ossificans progressiva: Although initial work indicated that ACVR1[R206H], as well as other FOP-associated variants of ACVR1, cause HO because they exhibit enhanced signaling either in the apparent absence or in the presence of certain BMPs (reviewed in [54]), it turned out that the key mechanism had been missed: FOP-causing ACVR1 variants drive HO in FOP by perceiving their own natural antagonist – Activin A – as an agonist, i.e. just like an osteogenic BMP.