The discovery of Toll-like receptors (TLRs) marked a pivotal moment in immunology, recognized by the 2011 Nobel Prize in Physiology or Medicine. TLRs are pattern-recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), playing a central role in innate immunity. The identification of TLRs began with the discovery of the IL-1 receptor (IL-1R) in mammals and the Toll protein in Drosophila. The mammalian TLR4 was later identified as the lipopolysaccharide (LPS) receptor, and subsequent studies elucidated the signaling pathways of TLRs, revealing their role in immune responses. TLRs are involved in both innate and adaptive immunity, with their signaling pathways including the MYD88 and TRIF pathways. TLRs recognize various ligands, including bacterial flagellin, viral RNA, and bacterial DNA, and are involved in the recognition of endogenous ligands. TLR signaling leads to the activation of NF-κB and type I interferon pathways, which are crucial for immune responses. TLRs have also been implicated in disease, with therapeutic applications of TLR agonists and antagonists being explored. The study of TLRs has significantly advanced our understanding of innate immunity and its role in disease, highlighting the importance of TLRs in immune defense and inflammatory responses.The discovery of Toll-like receptors (TLRs) marked a pivotal moment in immunology, recognized by the 2011 Nobel Prize in Physiology or Medicine. TLRs are pattern-recognition receptors that recognize pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), playing a central role in innate immunity. The identification of TLRs began with the discovery of the IL-1 receptor (IL-1R) in mammals and the Toll protein in Drosophila. The mammalian TLR4 was later identified as the lipopolysaccharide (LPS) receptor, and subsequent studies elucidated the signaling pathways of TLRs, revealing their role in immune responses. TLRs are involved in both innate and adaptive immunity, with their signaling pathways including the MYD88 and TRIF pathways. TLRs recognize various ligands, including bacterial flagellin, viral RNA, and bacterial DNA, and are involved in the recognition of endogenous ligands. TLR signaling leads to the activation of NF-κB and type I interferon pathways, which are crucial for immune responses. TLRs have also been implicated in disease, with therapeutic applications of TLR agonists and antagonists being explored. The study of TLRs has significantly advanced our understanding of innate immunity and its role in disease, highlighting the importance of TLRs in immune defense and inflammatory responses.