Previous studies have largely used cell culture and in vivo models of HO that rely on exposure of wild-type cells to non-physiological levels of osteogenic BMPs, or over-expression of ACVR1(R206H) or ACVR1(Q207D)30, a constitutively active, ligand-independent engineered receptor that has not been observed in the FOP patient population11,12,31,38–42. Here, CLN5 is linked to fibrodysplasia ossificans progressiva.