Huntington’s disease is associated with low levels of the REST target BDNF (brain derived neurotrophic factor), and restoration of BDNF can effectively reverse the Huntington’s disease phenotype (Xie et al. 2010), suggesting Sirt1 and REST may exacerbate the disease by downregulation of BDNF. The gene discussed is BDNF; the disease is juvenile Huntington disease.