Papain-like cysteine proteases have been divided into two subfamilies represented by mammalian enzymes cathepsin L and cathepsin B, respectively. The recent determination of the three-dimensional structures of four cysteine protease proenzymes showed that the mechanism of inhibition of the activity by the proregions is the same in both subfamilies despite significant differences in the proregion lengths. Here we describe the structures of the proregions, their binding to cognate enzymes and analyze similarities and differences between them.