In short, PERK attenuates IRE1 via RPAP2 to abort failed ER-stress adaptation and trigger apoptosis, which may explain our result that IRE1 pathway was only activated in early and middle stage of emphysema, and may participant in intrinsic apoptotic pathways, and at the severe or called end stage of emphysema, receptor mediate extrinsic apoptosis pathway activation may be due to the PERK and RPAP2 pathways. This evidence concerns the gene EIF2AK3 and pulmonary emphysema.