The role of cuproptosis in periodontitis: Current advances and future perspectives

Periodontitis is a prevalent chronic inflammatory disease characterized by progressive destruction of the periodontal supporting tissues. Copper homeostasis maintains intracellular copper balance through sophisticated regulatory networks, and its dysregulation may promote cuproptosis, a form of regulated cell death driven by excessive intracellular copper accumulation. Emerging evidence indicates that cuproptosis contributes to periodontitis by impairing macrophage mitophagy, blocking autophagic flux, and modulating immune responses. In addition, cuproptosis-related genes (CRGs) regulate immune cell infiltration and inflammatory mediator production, and their expression levels are closely associated with periodontal pathogens. This review summarizes the molecular mechanisms underlying copper homeostasis and cuproptosis and discusses their roles in the pathogenesis and progression of periodontitis, highlighting potential therapeutic targets and future research directions.