Advances in the Study of NOD-Like Receptors in Common Otological Diseases

Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are integral components of the cytoplasmic pattern recognition receptors (PRRs) family, playing a crucial role in both innate immunity and inflammatory responses. Nucleotide-binding oligomerization domain–like receptors detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), activating multiple signaling pathways, including nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK), and triggering immune responses throughinflammasome activation. The NLR family contains 5 distinguishable subfamily classifications. The development and progression of multipleear-related disorders depend significantly on NOD1, NOD2, NLRP3, and NLRX1, among other specific members of the NLR family. The analysisinvestigates NLRs’ interactions with ear pathologies, particularly focusing on NLRP3 functions in the development of otitis media along with itseffect on cholesteatoma formation and hearing loss. In addition, this review evaluates targeted therapeutic strategies derived from NLRs researchby developing a theoretical foundation that suggests new ways for advancing treatments for otological diseases.Cite this article as: Zhan L, Xu B, Bian P. Advances in the study of NOD-like receptors in common otological diseases. J Int Adv Otol. 2025, 21(5), 1940,doi:10.5152/iao.2025.251940.