Since the discovery of the b-secretase responsible for initiating the Alzheimer’s amyloid cascade as a novel membrane-bound aspartic protein-ase, termed ‘b-site amyloid precursor protein cleaving enzyme’, ‘aspartyl protease-2’ or ‘membrane-anchored aspartic proteinase of the pepsin family-2’, huge efforts have been devoted to an understanding of its biol-ogy and structure in the subsequent decade.