At the time when the terms were introduced, α-, β-, and γsecretases were activities known to cleave APP proteolytically, but not defined as specific enzymes performing the cleavage. It was later found that BACE-1 was responsible for β-secretase activity (Vassar et al., 1999) and that a complex of presenilin, nicastrin, Aph-1, and Pen-2 had γ-secretase activity Hooper, 2005) . The α-secretase cleavage was found to be mediated by zinc metalloproteases of the disintegrin and metalloprotease (ADAM) family, specifically ADAM10 and ADAM17 (also known as TNFα converting enzyme, TACE). ADAM10 was found to be the dominant enzyme of APP processing in SH-SY5Y cells, given a lesser effect of ADAM17 knockdown (Allinson et al., 2004) . Recent investigations have suggested that ADAM10 is the principal APP secretase in primary neurons, with ADAM17 playing more of an auxiliary role (Kuhn et al., 2010; Lichtenthaler, 2010) . Allinson et al. (2004) suggested a model whereby the group of metalloproteases would each contribute to greater or lesser extents to APP cleavage in different cells and under different conditions. The ADAMs have a wide number of substrates, including angiotensinconverting enzyme (ACE; Allinson et al., 2004) , ACE2 (Lambert et al., 2005) , the prion protein (Vincent et al., 2001) as well as each other ). The ADAMs have been reviewed in greater detail elsewhere (Allinson et al., 2003; Edwards et al., 2008; van Goor et al., 2009) .