Decapentaplegic (DPP) and bone morphogenetic protein (BMP)-2 and -4 type ligands form a branch of the transforming growth factor-beta (TGFbeta) superfamily. They play prominent roles in metazoan developmental processes as diverse as cell proliferation, apoptosis, differentiation and cell-fate determination. Maturation of the BMP2/4/DPP type proteins requires proteolytic cleavage of their proproteins by furin-type proprotein convertases (PCs). Even though cleavage of the prodomain is critical for signaling, much less attention has been paid to the role of proteolytic processing. Our studies suggest that the cleavage sites of BMP2/4/DPP type proteins have been diversified and can be categorized into at least four different types. These findings indicate that the cleavage sites in BMP2/4/DPP prodomains are tolerant to mutations acquired through evolution and have adapted to diversified environments among species. These results provide insights for further studies of evolution and molecular diversity. In this Extra View we discuss the evolutional variation seen in the sequences of BMP2/4/DPP type proteins.