The transcription factor interferon regulatory factor (IRF)-5 is a master regulator of inflammatory macrophage programming.8,9 Granulocyte macrophage colony-stimulating factor (GM-CSF) and interferon-γ treatment increases IRF5 expression.8,9 Toll like receptor activation of myeloid differentiation primary response gene 88 signaling leads to phosphorylation of IRF5 and its nuclear translocation.9 Genetic deletion of IRF5 protects from murine inflammatory arthritis and insulin resistance in diet-induced obesity,10,11 while its inhibition with nanoparticles decreases myocardial infarct size.12 The gene discussed is IRF5; the disease is Insulin resistance.