We speculated that the properly spatial and temporal control of the TBK1 kinase activity, as well as the phosphorylation levels of its substrates, and an optimum level of OPTN-mediated selective autophagy are crucial for maintaining cellular homeostasis, especially in neurons, and impaired autophagy is likely to contribute to the pathogenesis of neurodegenerative diseases caused by defective OPTN and TBK1. Here, OPTN is linked to neurodegenerative disease.