Additionally, NAMPT+ fibroblasts exhibited increased crosstalk with M2 macrophages through the C3-ITGB2 complement pathway, implicating NAMPT in promoting fibroblast activation and shaping a pro-fibrotic immune microenvironment.<h4>Conclusion</h4>This study identifies NAMPT as a critical regulator of cuproptosis in IPF fibroblasts and highlights its dual role in fibroblast activation and immune modulation. Here, ITGB2 is linked to idiopathic pulmonary fibrosis.