IRF5 and systemic lupus erythematosus: Indeed, multiple genome-wide association studies have identified IRF5 as one of the genes whose genetic variants are highly associated with SLE risk17,18; IRF5 encodes a transcription factor called IFN regulatory factor 5, which positively regulates endosomal Toll-like receptor (TLR)-mediated, myeloid differentiation primary response protein 88 (MyD88)-dependent innate immune responses19,20.