RIPK1 and neurodegenerative disease: In mammals, the RHIM domain was originally identified as a short amino acid sequence in the intermediate domain of RIPK1 (receptor-interacting serine/threonine protein kinase 1), and near the RIPK3 C-terminus that was pivotal to protein interactions and the promotion of necroptosis [5,6], a form of regulated necrosis triggered in ischemia-reperfusion injury (IRI), systemic inflammation, autoimmunity, and neurodegenerative diseases, among others [7–16].