OPTN and amyotrophic lateral sclerosis: Importantly, more recent studies revealed that genetic defects of TBK1, in particular, a TBK1 E696K missense variant and a deletion mutation lacking part of the TBK1 C-terminal domain (hereafter referred to as CTD) that is necessary to interact with adaptor proteins, including OPTN, NAP1, TANK and SINTBAD26, 33, are implicated in ALS pathogenesis19, 20.