OPTN and amyotrophic lateral sclerosis: Protein aggregates into neurons and glial cells are common features of amyotrophic lateral sclerosis (ALS) pathology, and have a key role in ALS initiation and progression: TDP43 proteinopathy is a hallmark of >95% of sporadic/nonmutated ALS.[1,2] Protein degradation machinery and autophagy have a crucial role in dealing with misfolded aggregated proteins.[3] In ALS several genes (UBQLN2, SQSTM1, OPTN, VCP, TBK1) have strong links with protein degradation pathways as their products contribute to recruitment of ubiquitinated proteins to the autophagosome.