In summary, the key contributions of this study include: (1) identification of MUC1 as a suppressor of PM2.5-induced airway inflammation; (2) demonstration that MUC1 attenuates inflammatory signaling via the TLR4/IRAK4/NF-κB axis; and (3) elucidation of MUC1’s role in inhibiting pyroptosis through downregulation of the NLRP3/GSDMD pathway. Here, MUC1 is linked to inflammation.