Emerging evidence reveals that the orexinergic system is disturbed in various neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and multiple sclerosis (MS), whereas the dysregulation of orexins and/or orexin receptors contributes to the pathogenesis of these diseases. Here, HCRT is linked to Huntington disease.