Current understanding of the mechanism of action of luspatercept. The SMAD-2/3 signaling pathway is the target of activin receptor ligand trap molecules. Members of the TGF-β superfamily ligand binding lead to the multimerization of type 1 and 2 receptors. Upon the activation of the type 1 receptor, phosphorylation of SMAD-2 and SMAD-3 takes place. Luspatercept prevents the binding of the ligand, thus inhibiting this pathway and promoting late-stage erythropoiesis.