Treatment with Nec-1 was reported to be neuroprotective in cerebral ischemia4 and brain trauma.43 Furthermore, Nec-1 has been shown to be efficacious to target the necroptosis pathway in animal models of Huntington disease (HD)44 and Amyotrophic lateral sclerosis (ALS).45 In this review, we investigate the role of necroptosis in neurodegenerative disorders and evaluate the potential of inhibiting necroptotic signaling pathway as a therapy for neurodegenerative disorders. This evidence concerns the gene PCSK1 and juvenile Huntington disease.