Mechanistically, GSDMD‐CT, released upon virus infection, interacts separately with retinoic acid‐inducible gene I (RIG‐I) and tank‐binding kinase (TBK1), promoting the selective autophagic degradation of RIG‐I via K48‐linked polyubiquitination at Lys181 and TBK1 via K27‐linked polyubiquitination at Lys487 by the E3 ligase TRIM28, which serves as a recognition signal for the cargo receptor NDP52 and TOLLIP, respectively. Here, CALCOCO2 is linked to viral infectious disease.