Objective: To explore the mechanism of MT-RNR2-like protein 1 (MTRNR2L1)-mediated regulation of PANoptosis during the development of Chronic Obstructive Pulmonary Disease (COPD), and to provide new ideas for finding the pathogenesis of COPD. Methods: Bulk RNA Sequencing (Bulk RNA-seq) data and Single Cell RNA Sequencing (scRNA-Seq) data from COPD patients in Gene Expression Omnibus (GEO) were used to explore the cellular composition in COPD patients' lung tissues and to analyse the pathways involved in the development of the disease. PANoptosis was simulated in smoke/lipopolysaccharide (LPS)-exposed mice, and MTRNR2L1 and PANoptosis protein expression was assessed to clarify their roles in the development of COPD. Results: Bulk RNA-seq demonstrated altered expression of T cell response-related genes in COPD patients. Single-cell RNA-seq confirmed decreased CD8+ T cells and increased epithelial cells compared to controls. The anti-apoptotic gene MTRNR2L1 was upregulated in COPD patient immune and epithelial cells. PANoptosis-related genes were reduced in lungs, CD8+ T cells and epithelial cells of COPD patients; Smoke/LPS-exposed mouse lungs exhibit alveolar damage, increased PANoptosis proteins, while MTRNR2L1 overexpression significantly inhibited cellular PANoptosis and downregulated the levels of ZBP1, Caspase-3, GSDMD, and MLKL.Conclusion: The differentially expressed genes in CD8+ T cells and epithelial cells were enriched in pathways related to PANoptosis , suggesting the involvement of PANoptosis in the development of COPD. The process of PANoptosis in the onset and development of COPD was associated with increased expression of PANoptosis-related proteins. MTRNR2L1 exhibited an inhibitory effect on PANoptosis, and regulating PANoptosis may provide new therapeutic opportunities for reducing lung injury and improving lung ventilatory function.