Our group recently discovered that the lysosomal aspartyl protease, cathepsin D (CatD) [11,12,13] is, by several measures, the principal protease responsible for degrading intracellular pools of the amyloid β-protein (Aβ) [14], which accumulates abnormally in Alzheimer disease (AD) [15]. This evidence concerns the gene CTSD and early-onset autosomal dominant Alzheimer disease.