IRF5 and autoimmune disease: IRF5 is a central regulator of inflammatory responses, polarising macrophages towards a pro-inflammatory phenotype and participating in various inflammatory and autoimmune diseases.2 SIGLEC5, an immune receptor recognising lipid ligands, modulates innate immune responses.51 Notably, genetic variants in SIGLEC5 have been directly linked to the risk for periodontitis,38 providing a strong validation that our oral frailty factor is capturing clinically relevant signals from its constituent traits.