Therefore, we speculated that dysfunctions of OPTN UBAN domain caused by those ALS-linked OPTN mutations such as E478G and defective interaction of TBK1 with OPTN induced by the ALS-linked TBK1 E696K mutation should lead to a common consequence, affecting the OPTN-dependent aggrephagy and mitophagy, which are two selective autophagy processes highly related to neurodegenerative diseases16, 42. Here, OPTN is linked to amyotrophic lateral sclerosis.