Several single-nucleotide polymorphisms (SNPs) and small insertions/deletions in the IRF5 gene or regulatory regions have been validated to independently cause different autoimmune diseases by altering gene expression, splicing, and RNA stability24–28, but whether there are other fine-scale molecular mechanisms that shape the pleiotropic effect at the IRF5 locus requires in-depth investigation. The gene discussed is IRF5; the disease is autoimmune disease.