Beta-secretase 1 (BACE1, memapsin-2) mediates the proteolytic processing of amyloid precursor protein (APP). BACE1 is transported from the plasma membrane to endosomes where APP hydrolysis takes place. The acid-cluster-dileucine (ACDL) motif in the cytosolic domain of BACE1 is able to bind to the VHS domain of ADP-ribosylation factor-binding proteins 1, 2 and 3 (GGA1,2,3) which play a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. This is the presumed recognition step for BACE1 transport to endosomes (He et al. 2003).