Reminiscent of ALS/FTD pathology, TMEM106B deficiency causes accumulation of ubiquitinated proteins and SQSTM1/p62 as well as phosphorylated TDP-43 in the brain and spinal cord of mouse models (Feng et al., 2020, 2022; Lüningschrör et al., 2020) and is associated with increased TDP-43 proteinopathy in human ALS brain (Mao et al., 2021). Here, TMEM106B is linked to amyotrophic lateral sclerosis.