TBK1 is a serine/threonine kinase essential for innate immune responses to viral and bacterial pathogens 1. Upon toll-like receptor activation, TBK1 associates with adaptor proteins TRAF3 and TANK to phosphorylate interferon regulatory factors IRF3 and IRF7, enabling their homodimerization and nuclear translocation to drive type I interferon production 12. TBK1 initiates IRF3 activation by phosphorylating scaffolding proteins MAVS, STING1, and TICAM1 on their pLxIS motifs, licensing them for subsequent IRF3 recruitment and phosphorylation 2. TBK1 also functions redundantly with IKKε to activate NF-κB signaling, though IRF3 activation shows greater kinase dependence 3. Beyond antiviral immunity, TBK1 regulates selective autophagy through optineurin phosphorylation, mTORC1/2 signaling, and TNF-induced cell death prevention via RIPK1 phosphorylation 4. TBK1 exhibits oncogenic properties in KRAS-mutant cancers, where it activates anti-apoptotic NF-κB signaling 5. Clinically, TBK1 haploinsufficiency causes amyotrophic lateral sclerosis and frontotemporal dementia 6, while aberrant activation contributes to autoinflammatory diseases. Age-related TBK1 dysregulation via reduced SIRT5-mediated desuccinylation promotes skeletal muscle degeneration 7.