A consistent finding across studies is the increased expression and extracellular release of HMGB1 in CRS tissues and nasal secretions, particularly in eosinophilic CRSwNP [45,46,47], and its contribute to inflammation, epithelial–mesenchymal transition (EMT), and tissue remodeling [48,49,50] through its interaction with RAGE and TLR4/9 signaling pathways, promoting cytokine release (IL-6, IL-8, TNF-α) and immune cell recruitment. This evidence concerns the gene TLR4 and congenital rubella syndrome.