A study has demonstrated that USP15 deubiquitinates TRIM25, thus counteracting the LUBAC‐dependent degradation of TRIM25.[181] Mechanistically, USP15 interacts with TRIM25 during the late stage of a viral infection, removes the LUBAC‐induced K48‐linked polyubiquitination of TRIM25 at its SPRY domain, and ultimately leads to sustained type I IFN expression. The gene discussed is TRIM25; the disease is viral infectious disease.