TARDBP and amyotrophic lateral sclerosis: For example, while ubiquitin-binding optineurin mutations Optn478G and OptnD474N failed to clear the overexpressed mutant TDP-43 in N2A neuronal cell line through autophagy, an ALS patient carrying a heterozygous mutation Optn478G did not test positive for TDP-43-positive autophagic vacuoles, unlike the patient carrying the homozygous OptnQ398X mutation who did [33,43].