In this study, we focused on the ER quality control protein KDEL receptor (KDELR) and demonstrated that KDELR2 and MUC5AC were colocalized in the airway epithelium of COPD patients and COPD model rats. In addition, knockdown of KDELR2 markedly reduced the expression of MUC5AC both in vivo and in vitro and knockdown of ATF6 further decreased the levels of KDELR2. Here, ATF6 is linked to chronic obstructive pulmonary disease.