Expression, Regulation and Therapeutic Implications of Nod-Like Receptors in Endodontics: A Narrative Review.

BACKGROUND: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are critical intracellular pattern recognition receptors that orchestrate innate and adaptive immune responses. Their dysregulated activation is mechanistically linked to the pathogenesis of numerous inflammatory diseases. In endodontics, pulpitis and apical periodontitis represent highly prevalent inflammatory conditions, primarily caused by bacterial invasion, which significantly impact patients' quality of life. Current studies demonstrate that NLR-mediated immunity plays a significant role in driving pulpal inflammation and periapical bone resorption. OBJECTIVES: This review aims to systematically synthesize current knowledge on the expression, regulatory mechanisms and functional roles of NLRs in dental pulp and periapical tissues. Furthermore, it seeks to critically evaluate the therapeutic potential of targeting NLR pathways for the management of endodontic diseases. METHOD: This narrative review employed a systematic search strategy. A comprehensive literature search was conducted across MEDLINE/PubMed and Scopus databases from inception to January 2026. Search terms combined concepts related to NLRs (covering all subfamilies and members, e.g., 'NOD-like receptors', 'NLRP3', 'NLRP6', 'NLRP12', 'NOD1', 'NOD2') and endodontics ('pulpitis', 'apical periodontitis', 'endodontic disease'). Relevant original research articles in English were included for narrative synthesis. RESULTS: The review delineates the structural characteristics and signalling pathways of NLRs, citing 48 articles. It details their specific expression patterns and functional roles within the specialized microenvironments of the dental pulp and periapical tissues. The analysis also surveys a promising landscape of NLR-targeted therapeutic strategies, including small-molecule inhibitors, biologics, nanotechnology-based delivery systems and genetic engineering. CONCLUSION: NLRs are pivotal regulators of the host immune response in endodontic diseases. A deeper understanding of their expression and mechanisms offers novel insights into disease pathogenesis. Modulating NLR pathways presents a promising, though challenging, therapeutic frontier for developing more effective treatments for pulpitis and apical periodontitis.