However, in the light of recent reports indicating that inhibition of SIRT2 is either detrimental or has no positive effects on neurodegenerative disorders such as ALS or cerebral ischemia [1], the fact that pharmacological and/or genetic inhibition of SIRT2 ameliorates pathology in models of AD and PD raises a double question: What is the molecular basis for this selectivity? The gene discussed is SIRT2; the disease is brain ischemia.