Our study of transforming genes led us to the identification of a new protein module, the WW domain, that is found in a wide range of structural, regulatory and signaling proteins. The WW domain is functionally similar to the SH3 module, in that it binds polyproline containing ligands. However, its structure is distinct. Unexpectedly, the WW domain-polyproline ligand connection was recently implicated in several human genetic disorders including the Mendelian form of hypertension known as Liddle's syndrome, and indirectly in muscular dystrophy, Alzheimer's disease and also in limb and kidney formation. Since both the WW domain and the core motif of its ligand are relatively short (40 and 5 amino acid residues), one could suggest that human diseases that involve mutations of these sequences could be treated successfully, not only by gene therapy approaches, but also by low molecular weight compounds. The rigid molecular shapes represented by the polyproline cores of the WW domain ligands could serve as guides for rational drug design.