TGFBR1 and fibrodysplasia ossificans progressiva: Type-I receptors (ALKs) are pivotal in determining signaling specificity within TGF-β superfamily pathways: Tgfbr1 (Alk5) serves as the primary receptor responsible for phosphorylating Smad2/3; Alk1(AVRL1), though largely endothelial-specific, also contributes to the non-canonical Smad1/5/8 pathway within the bone vasculature39; and Alk2 (ACVR1), unique among type-I receptors in its ability to bind both activin and BMP ligands,40 plays a critical role in the pathogenesis of fibrodysplasia ossificans progressiva (FOP).