Mutant HTT has been shown to bind and disrupt the functions of general transcription factors and transcriptional regulators in HD (Dunah et al., 2002; Luthi-Carter et al., 2002; Bae et al., 2005; Zhai et al., 2005) and has impaired capacity to interact with RE1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF), which alters the expression of many neuronal genes including brain-derived neurotrophic factor (BDNF; Zuccato et al., 2003, 2007). The gene discussed is REST; the disease is Huntington disease.