While MARCH5 is involved in the removal of proteins associated with specific neurodegenerative disorders such as ataxin-3 in Machado–Joseph disease or mSOD1 in amyotrophic lateral sclerosis likely supporting mitochondrial function, MARCH5 activity during general mitochondrial oxidative stress does not seem to confer a protective effect. The gene discussed is MARCHF5; the disease is amyotrophic lateral sclerosis.