A large body of evidence obtained from in vivo animal models and in vitro human explants has confirmed that the activation of TLR2 and TLR4 by endogenous TLR ligands in arthritic joints can trigger the innate immune response and initiate the production of pro-inflammatory cytokines, chemokines, and proteases, which are proposed to be responsible for the perpetuating inflammation and joints destruction of RA [22, 57–60]. The gene discussed is TLR2; the disease is rheumatoid arthritis.