In the secretory pathway, quality control for the correct folding of proteins is 
largely occurring in the endoplasmic reticulum (ER), at the earliest possible 
stage and in an environment where early folding intermediates mix with 
terminally misfolded species. An elaborate cellular mechanism aims at dividing 
the former from the latter and promotes the selective transport of misfolded 
species back into the cytosol, a step called retrotranslocation. During 
retrotranslocation proteins will become ubiquitinated on the cytosolic side of 
the ER membrane by dedicated machineries and will be targeted to the proteasome 
for degradation. The entire process, from protein recognition to final 
degradation, has been named ER-associated protein degradation, or simply ERAD. 
Ubiquitin has well known functions in aiding late steps of substrate 
retrotranslocation and in targeting substrates to the proteasome. Recent results 
show that several cytosolic machineries allow ubiquitinated substrates to 
undergo extensive remodeling, or processing, on their poly-ubiquitin chains 
(PUCs). Although still ill-defined, PUC processing might have a unique function 
for ERAD in that it might provide a mechanism to generate optimal PUCs for 
recognition by proteasomal ubiquitin receptors. Ubiquitination might also have a 
previously unanticipated role in quality control of ER membrane proteins. This 
review recapitulates the current knowledge and recent findings about 
ERAD-specific roles of ubiquitin.