RELA and Dravet syndrome: In fibroblasts from individuals with DS, small interfering RNA (siRNA) silencing of APPL1 corrects known endocytic anomalies3 and reverses elevated nuclear translocation of p65/RelA, an indication of activated NF-κB signaling,21 which is known to be mediated by APPL1/rab5 endosomes.16 Finally, we show, for the first time, that βCTF levels are elevated in AD despite normal APP levels, which is accompanied by abnormally high recruitment of APPL1 to rab5 endosomes in AD brain, similar to that seen in cells from individuals with DS.