Notably, this study represents the first to engineer a transgenic mouse model overexpressing the human MUC5B rs35705950 variant in the proximal large airways and to demonstrate that mucin overexpression linked to the MUC5B promoter polymorphism rs35705950, a significant genetic risk factor for idiopathic pulmonary fibrosis (IPF), paradoxically exerts protective effects against lung fibrosis and inflammation. Here, MUC5AC is linked to idiopathic pulmonary fibrosis.