Given the crucial role attributed to upregulated PDE activity in the pathobiology of asthma, these new findings highlight a heretofore-unidentified decisive role for Gβγ signaling in regulating the heightened PDE4 activity that characterizes the asthmatic airway, and suggest that interventions targeted at suppressing Gβγ signaling associated with Gi protein activation may lead to novel approaches to treat asthma. This evidence concerns the gene GNAI1 and asthma.