RGS4 immunoreactivity was more extensive in asthmatic versus normal bronchial epithelium and increased proportionally with disease severityMUC5AC expression correlated with RGS4 expressionPGE2 was detected at higher levels in BALF from AF‐exposed mice versus controls and levels were even higher when RSG4 was knocked down. AF challenge caused increased PGE expression through PAR2 activationPAR2 mediated bronchodilation through an RGS4‐regulated pathway in mice. RGS4 inhibited PGE2 secretion by limiting GPCR‐induced G protein activation upstream of PGE2 biosynthesis. The gene discussed is RGS4; the disease is atrial fibrillation.