APPL1 and Dravet syndrome: We next investigated the pathogenic importance of APPL1 alterations in fibroblasts from individuals with DS, where elevated βCTF induces rab5 activation and diverse endosome anomalies.3, 8, 9 APPL1 colocalized with rab5-positive endosomes to a significantly greater degree in DS fibroblasts compared with that in control cells (Figure 5a), consistent with APPwt overexpression in N2a cells (Supplementary Figure 2a) and suggesting that APP overexpression in DS cells recruits more APPL1 to rab5 endosomes.