•FTLD brain was highly immunoreactive for TDP-43 inclusions.•TDP-43 is full length (N-/C-terminal) and highly acetylated in ALS's TDP-43 inclusions.•Changes in acetylation plays an important role in loss of function and accumulation of TDP-43 in stress granules. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.