Tank-binding kinase 1 (TBK1; EC 2.7.11.1) functions as a key node protein in several cell signaling pathways, including innate immune response, xenophagic elimination of bacteria and, under pathological conditions, cell growth and proliferation. TBK1 is composed of a kinase domain (KD) that houses its catalytic activity and three accessory/regulatory elements: a ubiquitin-like domain (ULD), a dimerization domain (DD) and a small protein interaction module at the C-terminus. Upon pathway stimulation, TBK1 is recruited to signaling complexes via its C-terminal AB motif. Here local clustering of TBK1 molecules can allow interdimer KD interactions that lead to trans-autophosphorylation. TBK1 has very recently been implicated as an upstream regulator in the autophagic clearance of protein aggregates associated with glaucoma and various neurodegenerative diseases, as well as a critical component of the elevated basal autophagy observed in KRAS-dependent non-small cell lung cancer (NSCLC).