Based on kinase-dead knock-in RIPK1 mice and highly selective allosteric Type 3 RIPK1 inhibitors (necrostatin-1 [Nec-1] and optimized analogue Nec-1s)14,15, RIPK1 is implicated in a variety of human diseases, such as ischemia-reperfusion injury in the brain16, heart17, and kidney18, acute and chronic inflammatory diseases19, multiple sclerosis (MS)20, and amyotrophic lateral sclerosis21. Here, RIPK1 is linked to multiple sclerosis.