BACE-1 was found to be palmitoylated at three residues, which indicated possible raft localization and interaction with raftresident lipids (Kalvodova et al., 2005; Hattori et al., 2006) . When BACE-1 was targeted to lipid rafts via GPI-anchoring, production of Aβ was increased, indicating upregulation of amyloidogenic APP processing (Cordy et al., 2003) . A more recent study suggests that GPI-anchorage increases preferential cleavage at the β-site of APP, producing the full length Aβ, whereas wtBACE-1 cleaves APP at two sites (β and β' sites) producing full length and N-terminally truncated Aβ (Vetrivel et al., 2011) . Another study has reported the effects of GPI-anchorage of ADAM10, the principal α-secretase, and showed that no wtADAM10 was raft localized while all GPI-ADAM10 was in lipid rafts. It was associated with a reduction in Aβ as GPI-ADAM10 competed with BACE-1 for the APP substrate .