Importantly, the critical implication of endoplasmic reticulum (ER) stress and unfolded protein response—in close relation with several pivotal cellular immune/inflammatory platforms including mitochondria, NLRP3 inflammasome, and phosphoinositide 3-kinase-δ—in the generation of corticosteroid resistance is now being increasingly demonstrated in numerous experimental settings of severe asthma. This evidence concerns the gene NLRP3 and asthma.