In search of an explanation as to how APP could be cleaved in two distinct (amyloidogenic and non-amyloidogenic) pathways, it was suggested that APP was present in two cellular pools (Ehehalt et al., 2003) as schematically presented in Figure 2 . Amyloidogenic processing was suggested to be linked to lipid rafts as their integrity was critical for Aβ formation (Simons et al., 1998; Cordy et al., 2003; Ehehalt et al., 2003; Rushworth and Hooper, 2011) and Aβ production was also indicated to be raft-localized (Lee et al., 1998) . Furthermore, the precise protein/lipid composition of the rafts was shown to influence Aβ release (Lemkul and Bevan, 2011) and aggregation (Ikeda et al., 2011) . Tetraspanins were also shown to regulate APP processing (Yanez-Mo et al., 2011) and perturbation of tetraspanin enriched domains (TEMs) can affect cell signaling pathways (Hemler, 2005) . For example, the α-secretase ADAM10 is regulated by tetraspanins and in this way, tetraspanins can affect the non-amyloidogenic processing of APP (Arduise et al., 2008) . In addition to this, tetraspanins also regulate the amyloidogenic pathway of APP processing since γ-secretase was shown to be associated with TEMs (Wakabayashi et al., 2009 ).