Therefore, unlike TDP-43 and FUS, two RBPs whose cytoplasmic mislocalization is tightly tied to neurodegeneration in ALS/FTD models, cytoplasmic MATR3 retention mitigates toxicity, suggesting that nuclear MATR3 functions are required for neurodegeneration (Barmada et al., 2010b; Qiu et al., 2014). The gene discussed is MATR3; the disease is amyotrophic lateral sclerosis.