Figure 1 TLR-targeted genetic polymorphisms, mechanism and drug application in three RA pathological manifestations. SNPs in TLR4 (rs4986790, rs4986791, rs1927911, rs11536878) and TLR2 (rs5743708) are indicated, which may affect TLR-mediated signaling cascades, downstream cytokine production, and genetic predisposition to RA. And the pharmaceuticals have been developed and to exert a therapeutic effect on RA by targeting TLRs, as follows. (a) Targeting TLR2, TLR4 and TLR7 in synovial inflammation, with drugs including OPN-305, crocin, resveratrol, scoparone, carvedilol, AVR-25, TAP2, PIP2, cPIP2, sulforaphane, the oxazolidinone derivative OSL07, NI-0101, caffeic acid phenethyl ester, arctiin, nicorandil, diclofenac, astragali polysaccharide, rosemary, salvia, and imiquimod. (b) Targeting TLR2 or TLR5 in vascular pannus, with drugs including OPN-301. (c) Targeting TLR3/4 and TLR7/8/9 in cartilage and bone destruction, with drugs including auranofin, mianserin, fluoxetine, citalopram, mangiferin, chloroquine, hydroxychloroquine, and quinacrine. (d) The investigational drug represents the potential pharmaceutical or target in research. TLR, toll-like receptor; RA, rheumatoid arthritis; SNP, single-nucleotide polymorphism.