Terminally misfolded or unassembled proteins are degraded by the cytoplasmic 
ubiquitin-proteasome pathway in a process known as ERAD (endoplasmic 
reticulum-associated protein degradation). Overexpression of ER 
alpha1,2-mannosidase I and EDEMs target misfolded glycoproteins for ERAD, most 
likely due to trimming of N-glycans. Here we demonstrate that overexpression of 
Golgi alpha1,2-mannosidase IA, IB, and IC also accelerates ERAD of terminally 
misfolded human alpha1-antitrypsin variant null (Hong Kong) (NHK), and mannose 
trimming from the N-glycans on NHK in 293 cells. Although transfected NHK is 
primarily localized in the ER, some NHK also co-localizes with Golgi markers, 
suggesting that mannose trimming by Golgi alpha1,2-mannosidases can also 
contribute to NHK degradation.