As acetylation, along with other PTMs, is a key feature of TDP-43 pathology in ALS and FTD, we next sought to determine whether sequestration of endogenous TDP-43 to acetylation-mimicking mutant TDP-43 structures altered its solubility or mobility, indicating dysfunction and pathological transition. This evidence concerns the gene TARDBP and amyotrophic lateral sclerosis.