Thus, in both the C9-AAV mouse model and C9-ALS human tissue, cells that have TMEM106B positive punctate-like structure have a decreased TDP-43 nuclear to cytoplasmic ratio, suggesting a potential relationship between abnormal TMEM106B pathology and TDP-43 mislocalization in C9-ALS and C9-ALS/FTD in humans. Here, TMEM106B is linked to amyotrophic lateral sclerosis.