Unlike wild-type OPTN, the ALS-associated mutant (with a mutation in the ubiquitin-associated domain [E478G]) and LIR mutant of OPTN cannot restore OPTN deficiency-impaired mitochondrial turnover, suggesting the detrimental role of OPTN deficiency in defective mitophagy-linked neurodegenerative diseases [340,342]. This evidence concerns the gene OPTN and neurodegenerative disease.