Limited endoproteolysis of biologically inactive polypeptide precursors is a general mechanism generating a diversity of biologically active peptides and proteins in all eukaryotic phyla. One of the major recognition motifs involves cleavage at either specific single or pairs of basic residues of the general formula (R/K) - Xn - (R/K) decreases, where n = 0, 2, 4 or 6. Such sites are found in a variety of protein precursors in all eukaryotes, including those of endocrine and neural polypeptide hormones, enzymes, growth factors, receptors, adhesion molecules, viral glycoproteins, coagulation factors and even cell signaling molecules. A family of seven mammalian proteinases responsible for the processing of these proproteins has been recently identified. It comprises the proprotein convertases PC1/PC3, PC2, furin/PACE, PC4, PACE4, PC5/PC6 and PC7/SPC7/LPC/PC8. In a combinatorial fashion, these enzymes determine the cell-type and time at which biologically active products are derived from a given inactive precursor protein, thereby profoundly affecting cellular communication, differentiation and metabolic activity.