Consequently, while the value of the study by Ye et al. (2019) for the structural biological understanding of TBK1 function is undisputable, their conclusion that impairment of various different cell biological TBK1 functions may result in ALS/FTD is based on analyses of “variants of unknown significance” and is currently not supported by genetic evidence. Here, TBK1 is linked to amyotrophic lateral sclerosis.