Interferon regulatory factor 5 (IRF5) is a transcription factor activated downstream of Toll-like receptors (TLRs) 7, 8 and 9, and is predominantly expressed in dendritic cells, B cells, monocytes and macrophages. Once considered an undruggable target, IRF5 is now recognized as a key regulator of innate immunity, driving the production of type I interferons, pro-inflammatory cytokines and autoantibodies.