BTK and viral infectious disease: In sum, our work highlights the important role of BTK-DDX41-STING signaling in the innate immune response against CMV, which the virus subverts by attenuating its cytoplasmic activity, thereby diverting it from its typically protective function.<h4>Importance</h4>Human cytomegalovirus (CMV) is an ubiquitous pathogen that poses a significant threat to immunocompromised individuals, highlighting the critical role of innate immunity in controlling this viral infection.