These findings collectively support our hypothesis that calcium signaling serves as a crucial bridge connecting C5a/C5aR1 signaling to the upregulation of ACSL4 in pulmonary fibrosis, positioning ACSL4 as a key regulatory node integrating signals from both the C5a/C5aR1 and TGF-β signaling in the pathogenesis of fibrosis. Here, C5AR1 is linked to pulmonary fibrosis.