The presenilin complex, consisting of presenilin, nicastrin, anterior pharynx defective-1 and presenilin enhancer-2, constitutes c-secretase, which is required for the generation of amyloid b-protein. In this article, we show that Synoviolin (also called Hrd1), which is an E3 ubiquitin ligase implicated in endoplasmic reticulum-associated degradation