Studies in chronic smokers and COPD patients have shown that ER stress and UPR activation have occurred by measuring relevant markers, including GRP78, PERK, eIF2α and CHOP, indicating a possible role of ER stress and prolonged UPR activation that result in cell death and COPD (Malhotra et al., 2009; Geraghty et al., 2016). This evidence concerns the gene EIF2AK3 and chronic obstructive pulmonary disease.