HTT (and mHTT) is a large protein that interacts with many binding partners2, and a number of key pathogenic mechanisms have been described in HD, including aberrant caspase activation, mitochondrial dysfunction3–7, ER stress, transcriptional dysregulation, altered calcium signaling, proteasome inhibition, defects in vesicle transport, and altered neurotransmitter release and activity1,3,4. The gene discussed is HTT; the disease is Huntington disease.