蛋白质正确折叠是细胞健康的基础；因此，内质网（ER）中错折叠蛋白质的积累导致内平衡失调，造成ER压力。各种研究表明，蛋白质误折叠是很多人类疾病的发病重要因素，包括癌症、糖尿病和囊性纤维化。ER中错折叠蛋白质的积累会启动复杂的信号转导途径——未折叠蛋白质反应（UPR），该途径由控制ER内部的三种蛋白质IRE1α、PERK和ATF6控制。简单地说，当ER压力无法逆转时，IRE1α会诱导炎症前体蛋白的激活；PERK会磷酸化eIF2α，促进ATF4基因的转录；而ATF6会激活编码ER分子伴侣蛋白的基因。网络压力会改变钙离子的平衡，钙离子从ER中释放，被线粒体吸收，导致氧自由基的产生增加，从而导致氧化压力。细胞内钙离子的积累，加上致命的活性氧水平，与炎症过程的启动和炎症前体蛋白的表达增加有关。Lumacaftor（Vx-809）是治疗囊性纤维化的常用矫正剂，可增强突变的F508del-CFTR的折叠，该蛋白质是导致该病的最普遍损伤蛋白质之一，从而促进突变蛋白质在细胞膜上的更高定位。我们在这里展示了这种药物减轻ER压力以及由此引起的炎症现象。因此，这种分子是治疗由蛋白质聚集造成慢性网络压力的几种疾病的有前途的药物。

Correct protein folding is the basis of cellular well-being; thus, accumulation of misfolded proteins within the endoplasmic reticulum (ER) leads to an imbalance of homeostasis that causes stress to the ER. Various studies have shown that protein misfolding is a significant factor in the etiology of many human diseases, including cancer, diabetes, and cystic fibrosis. Misfolded protein accumulation in the ER triggers a sophisticated signal transduction pathway, the unfolded protein response (UPR), which is controlled by three proteins, resident in ER: IRE1α, PERK, and ATF6. Briefly, when ER stress is irreversible, IRE1α induces the activation of pro-inflammatory proteins; PERK phosphorylates eIF2α which induces ATF4 transcription, while ATF6 activates genes encoding ER chaperones. Reticular stress causes an alteration of the calcium homeostasis, which is released from the ER and taken up by the mitochondria, leading to an increase in the oxygen radical species production, and consequently, to oxidative stress. Accumulation of intracellular calcium, in combination with lethal ROS levels, has been associated with an increase of pro-inflammatory protein expression and the initiation of the inflammatory process. Lumacaftor (Vx-809) is a common corrector used in cystic fibrosis treatment which enhances the folding of mutated F508del-CFTR, one of the most prevalent impaired proteins underlying the disease, promoting a higher localization of the mutant protein on the cell membrane. Here, we demonstrate that this drug reduces the ER stress and, consequently, the inflammation that is caused by such events. Thus, this molecule is a promising drug to treat several pathologies that present an etiopathogenesis due to the accumulation of protein aggregates that lead to chronic reticular stress.