The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a crucial role in detecting RNA viruses and initiating antiviral immunity. These receptors detect viral RNA or processed self-RNA in the cytoplasm, triggering innate immunity and inflammation. RLRs cooperate with Toll-like receptors and other factors to modulate adaptive immune responses. Regulation of RLRs occurs at various levels, including autoregulation, ligand and co-factor interactions, and post-translational modifications. Abnormal RLR signaling or dysregulation of RLR expression is implicated in autoimmune diseases. Understanding RLR signaling can guide targeted therapeutics for antiviral and immune-modulating applications. RIG-I and MDA5 detect various viruses and signal IFN production through the adaptor IPS-1. The RLR signaling pathway involves complex interactions with other immune pathways, such as TNFR1 and TLR signaling, and is regulated by post-translational modifications like ubiquitination and phosphorylation. RLRs also cooperate with other PRRs to enhance the immune response against viruses. Additionally, RLRs regulate the adaptive immune response, influencing T cell survival, B cell differentiation, and antibody production. Polymorphisms in RLR genes are associated with susceptibility to autoimmune diseases.The RIG-I-like receptors (RLRs) RIG-I, MDA5, and LGP2 play a crucial role in detecting RNA viruses and initiating antiviral immunity. These receptors detect viral RNA or processed self-RNA in the cytoplasm, triggering innate immunity and inflammation. RLRs cooperate with Toll-like receptors and other factors to modulate adaptive immune responses. Regulation of RLRs occurs at various levels, including autoregulation, ligand and co-factor interactions, and post-translational modifications. Abnormal RLR signaling or dysregulation of RLR expression is implicated in autoimmune diseases. Understanding RLR signaling can guide targeted therapeutics for antiviral and immune-modulating applications. RIG-I and MDA5 detect various viruses and signal IFN production through the adaptor IPS-1. The RLR signaling pathway involves complex interactions with other immune pathways, such as TNFR1 and TLR signaling, and is regulated by post-translational modifications like ubiquitination and phosphorylation. RLRs also cooperate with other PRRs to enhance the immune response against viruses. Additionally, RLRs regulate the adaptive immune response, influencing T cell survival, B cell differentiation, and antibody production. Polymorphisms in RLR genes are associated with susceptibility to autoimmune diseases.