Targeting cu metabolism as a potential therapeutic strategy for pulmonary fibrosis

Cuproptosis, a recently identified form of programmed cell death driven by copper (Cu) ions, has gained attention owing to its involvement in metabolic disorders and degenerative conditions. Pulmonary fibrosis, characterized by abnormal extracellular matrix accumulation and gradual deterioration of lung function, persists as a lethal disorder with few effective treatments. Dysfunctions in Cu metabolism or regulatory pathways lead to an imbalance in pulmonary Cu homeostasis, thereby influencing the onset and progression of lung diseases. These findings have renewed the interest in the role of cuproptosis in pulmonary fibrosis. However, given that research on cuproptosis in the field of pulmonary fibrosis is in its early stages, our current understanding of its role in this condition is limited. Thus, this review summarizes the biochemical pathways underlying cuproptosis, discusses its possible contribution to the development of pulmonary fibrosis, and presents therapeutic strategies focused on modulating Cu homeostasis. Although conclusive data directly associating cuproptosis with pulmonary fibrosis remain limited, growing evidence highlighting Cu imbalance, mitochondrial impairment, and dysregulated cell death mechanisms strengthens the need for deeper exploration in this field. Future research may pave the way for developing novel therapeutic approaches targeting Cu metabolism to address the unmet clinical needs of patients with pulmonary fibrosis.