In the lungs, the two major airway mucins secreted into airspaces are MUC5AC and MUC5B. In human asthma, both mucins are expressed at similar levels. In mice, Muc5ac is required for the development of asthma-like airflow obstruction. In this discovery, the Evans lab reports that Muc5b is protective in a mouse asthma model. This is the first time showing Muc5b’s impact on lung function. This discovery shows that protection occurs through the specific glycosylation of Muc5b, and the effects of glycosylation on its biophysical properties. MUC5B expression levels vary significantly in humans due to heterogeneity in the gene encoding this mucin. In people with asthma, airway hyperresponsiveness to MCh is also associated with the absence of MUC5B in individuals with the greatest allergic symptoms. Enhancing MUC5B levels and/or function via its sialylation could be beneficial in asthma patients.