Simplified schematic representation of the TLR4 signaling pathway. Upon interaction with LPS via CD14 and MD2 (myeloid differentiation protein-2), TLR4 recruits the adaptor protein MyD88 and activates IRAK1 and IRAK4 via MyD88-controlled pathways. In combination with TRAF6 (TNFα receptor–associated factor-6), IRAKs activate TAK1 (TGFβ–activated kinase 1). This leads, via phosphorylation of IKKs (IκB kinases), to NF-κB activation and transcription of inflammatory cytokines. Professional illustration by Paulette Dennis.