SQSTM1 and amyotrophic lateral sclerosis: In this regard it is interesting to note that some patients with pathogenic variants in SQSTM1 do not develop PDB but instead present with neurological disease such as amyotrophic lateral sclerosis (ALS) as part of multisystem proteinopathy syndromes [28] The reason underlying these different presentations remains incompletely understood but there is evidence that digenic inheritance of more than one variant may play a role [29].