Innate immunity provides an instant protection against bacterial infection by detecting and responding to lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, which proceeds through a germline-encoded transmembrane pattern recognition receptor Toll-like receptor 4 (TLR4) (ESI-Fig. 1‡).1,2 TLR4 activation by LPS results in the induction of transcription factor NF-κB signaling leading to the upregulation of cytokines, chemokines and co-stimulatory molecules which generally facilitates recovery from infection. The gene discussed is TLR4; the disease is bacterial infectious disease.