Deregulation of TGF-β superfamily signaling is a causative factor in many diseases. Bivalent single-chain traps that neutralize TGF-β family ligands (green and orange) were rationally designed using native intrinsically disordered regions as linkers (black) between two cognate receptor binding domains (magenta). TGF-β traps designed by this innovative strategy can achieve similar or better in vitro potency and in vivo tumor growth inhibition compared to a neutralizing antibody, indicating their promising therapeutic potential. For details, see article by Zwaagstra and colleagues on page 1477.