Quality control mechanisms in the endoplasmic reticulum prevent deployment of 
aberrant or unwanted proteins to distal destinations and target them to 
degradation by a process known as endoplasmic reticulum-associated degradation, 
or ERAD. Attempts to characterize ERAD by identifying a specific component have 
revealed that the most general characteristic of ERAD is that the protein 
substrates are initially translocated to the ER and eventually eliminated in the 
cytosol by the ubiquitin-proteasome pathway. Hence, dislocation from the ER back 
to the cytosol is a hallmark in ERAD and p97/Cdc48p, a cytosolic AAA-ATPase that 
is essential for ERAD, appears to provide the driving force for this process. 
Moreover, unlike many ERAD components that participate in degradation of either 
lumenal or membrane substrates, p97/Cdc48p has a more general role in that it is 
required for ERAD of both types of substrates. Although p97/Cdc48p is not 
dedicated exclusively to ERAD, its ability to physically associate with ERAD 
substrates, with VIMP and with the E3 gp78 suggest that the p97/Cdc48Ufdl/Npl4 
complex acts as a coordinator that maintains coupling between the different 
steps in ERAD.