Increased transcription of orosomucoid like 3 (Ormdl3) is linked with nonallergic childhood-onset asthma. We developed a full and conditional knockout and a transgenic Ormdl3 overexpressing mouse model, which will allow us to carefully dissect its role in asthma. Mechanistically, we will focus our attention on sphingolipid metabolism, calcium homeostasis and the role of the unfolded protein response.