In some cases, a poorly conserved cleavage site may represent a pathological condition in the species where the cleavage was first identified. For example, despite there being few cleavages for cathepsin H, the reported cleavages in the BID protein (36) are in particularly poorly conserved regions (see Figure 3 ). Cleavage of the BID protein leads to the induction of apoptosis. That the cleavage sites are not well conserved amongst mammalian orthologues is not surprising given that the cytoplasmic substrate and the lysosomal peptidase should not meet under normal circumstances. The mouse protein in which the cleavage was identified may therefore be unusually susceptible to cleavage should the lysosomal membrane be ruptured.