Moreover, TDP-43 and FUS, the two major pathological proteins in ALS, both showed functional links to NEAT1. Using novel cell lines with the FUS gene modified by CRISPR/Cas9 and human patient fibroblasts, a previous study found that endogenous levels of mutant FUS caused accumulation of NEAT1 isoforms and paraspeckles, and further hypothesized that perturbed structure and functionality of paraspeckles accompanied by accumulation of non-paraspeckle NEAT1 may contribute to the disease severity in ALS-FUS [32]. The gene discussed is FUS; the disease is amyotrophic lateral sclerosis.