TANK is an adapter protein that functions as a negative regulator of NF-κB signaling and plays a critical role in antiviral innate immunity. Structurally, TANK constitutively binds TBK1 and IKBKE to regulate I-κB kinase (IKK) activity, maintaining TRAF proteins in a latent state and preventing TRAF2-mediated NF-κB activation downstream of CD40, TNFR1, and TNFR2 signaling. Mechanistically, TANK serves as a molecular scaffold that assembles ZC3H12A and USP10 into a deubiquitination complex, which attenuates NF-κB activation through deubiquitination of IKBKG or TRAF6 following IL-1β stimulation or DNA damage. Additionally, TANK promotes USP10-mediated deubiquitination of TRAF6 in response to DNA damage, providing negative feedback control over pro-survival pathways. Disease relevance includes roles in antiviral defense through type I interferon production and in suppressing aberrant NF-κB-dependent cell survival following genomic stress. Clinically, TANK dysfunction may contribute to inflammatory diseases, cancer susceptibility, or impaired antiviral responses, though direct therapeutic applications remain under investigation. The protein's multifaceted regulatory role positions it as a critical node in integrating innate immune and DNA damage responses.