IRE1β evolves to be a guardian of respiratory and gastrointestinal mucosa

Inositol-requiring enzyme 1 (IRE1), a mediator of the unfolded protein response, shows the highest degree of evolutionary conservation. Vertebrates express two IRE1 paralogs: IRE1α, which is universally expressed and IRE1β, which shows specific expression within mucus secreted cells in respiratory and gastrointestinal tracts. The biological properties and regulation of the two IRE1 duplicates show evolutionary differences. As recently suggested, IRE1β-deficient mice display impairment in secreted protein expression and mucosal homeostasis. Abnormal changes in IRE1β caused by external and internal factors can disrupt mucosal homeostasis and further lead to respiratory and gastrointestinal diseases. Here, we highlight the physiological functions of IRE1β in the respiratory and gastrointestinal tracts in response to environmental microbes, viruses, toxins, and food components.