Besides physiological relevance however, our finding that SIRT1 and SIRT5 are neuroprotective when expressed at elevated levels raises the possibility that increasing endogenous expression of these two proteins within vulnerable neuronal populations pharmacologically, or ectopically expressing them at high levels (using viral vectors for example) could represent viable therapeutic approaches to prevent neuronal loss in neurodegenerative diseases. Here, SIRT5 is linked to neurodegenerative disease.