Lung cells are constantly exposed to various internal and external stressors that disrupt protein homeostasis. To cope with these stimuli, cells evoke a highly conserved adaptive mechanism called the unfolded protein response (UPR). UPR stressors can impose greater protein secretory demands on the endoplasmic reticulum (ER), resulting in the development, differentiation, and survival of these cell types to meet these increasing functional needs. Dysregulation of the UPR leads to the development of the disease. The UPR and ER stress are involved in several human conditions, such as chronic inflammation, neurodegeneration, metabolic syndrome, and cancer. Furthermore, potent and specific compounds that target the UPR pathway are under development as future therapies. The focus of this review is to thoroughly describe the effects of both internal and external stressors on the ER in asthma. Furthermore, we discuss how the UPR signaling pathway is activated in the lungs to overcome cellular damage. We also present an overview of the pathogenic mechanisms, with a brief focus on potential strategies for pharmacological interventions.

肺细胞不断暴露于破坏蛋白质稳态的各种内部和外部压力源。为了应对这些刺激，细胞会引发一种高度保守的适应性机制，称为未折叠蛋白反应 (UPR)。UPR 压力源可以对内质网 (ER) 施加更大的蛋白质分泌需求，从而导致这些细胞类型的发育、分化和存活，以满足这些日益增长的功能需求。UPR的失调导致疾病的发展。UPR 和 ER 压力与多种人类疾病有关，例如慢性炎症、神经退行性变、代谢综合征和癌症。此外，针对 UPR 途径的有效和特异性化合物正在开发中，作为未来的治疗方法。本综述的重点是彻底描述内部和外部压力源对哮喘 ER 的影响。此外，我们讨论了如何在肺部激活 UPR 信号通路以克服细胞损伤。我们还概述了致病机制，并简要介绍了药物干预的潜在策略。