On the basis of our current structural data, those ALS-linked mutations located at the C-terminal part of OPTN are unlikely to affect the interaction between OPTN and TBK1, but more likely to disturb or disrupt the function of OPTN UBAN domain, which is critical for the OPTN-dependent selective autophagy processes22, 40. Here, TBK1 is linked to amyotrophic lateral sclerosis.