TLR3 (Toll-like receptor 3) is a key innate immune receptor that recognizes double-stranded RNA (dsRNA), a molecular pattern associated with viral infection 1. Upon activation, TLR3 signals exclusively through the TRIF adaptor protein to induce NF-κB activation and type I interferon (IFN-α/β) production, establishing antiviral host responses 21. TLR3 maintains constitutive IFN-β levels in human fibroblasts and cortical neurons, controlling basal expression of interferon-stimulated genes that provide cell-intrinsic antiviral immunity 3. Beyond classical immune functions, TLR3 exhibits tissue-specific roles including regulation of nasal epithelial extracellular vesicles that provide antiviral protection through miRNA delivery and direct virion neutralization 4. Notably, TLR3 can translocate to the nucleus in cancer cells where it promotes metastasis and chemoresistance through interactions with PRMT5 and c-Myc 5. TLR3 deficiency causes primary immunodeficiency with increased susceptibility to viral infections, particularly HSV-1 encephalitis, due to impaired CNS cell-intrinsic immunity 3. The receptor also shows developmental regulation with reduced expression and function in newborn versus adult immune cells 6. Genetic polymorphisms in TLR3 are associated with cancer risk, highlighting its broader pathological significance 7.