In this study, we demonstrate that loss of IL‐4Rα/PI3K signaling, via a mutation in the IL‐4R motif necessary for the recruitment of IRS‐1 and IRS‐2, does not increase severity or susceptibility in allergic disease but rather accelerates IgE/mast cell‐mediated, food‐induced anaphylaxis progression in mice. The gene discussed is IRS2; the disease is anaphylaxis.