RIPK1

RIPK1 is a stress-sensing serine/threonine kinase that coordinates cell survival, inflammatory signaling, apoptosis, and immunogenic cell death^[1]. Mechanistically, RIPK1 acts within TNF-related signaling complexes, where its scaffold function restrains caspase-8- and RIPK3-dependent lethality while its kinase activity promotes regulated cell death under defined stimuli^[2]. In necroptosis, RIPK1 cooperates with RIPK3 to assemble a phosphorylation-dependent complex, and RIPK3 phosphorylates MLKL to drive membrane-disruptive necrotic death^[3][4]. Compared with related RIPK3 and MLKL, RIPK1 is distinguished by separable kinase-dependent death signaling and kinase-independent scaffold protection, making isoform-specific interpretation essential in experimental design^[5][6]. Disease models link RIPK1 activity to ALS axonal degeneration, Alzheimer’s disease microglial responses, and human immunodeficiency or intestinal inflammation caused by RIPK1 loss of function^[7][8][9]. For experimental applications, necrostatins and clinical RIPK1 inhibitors provide tools to test kinase-dependent biology, but inhibitor selectivity and scaffold-preserving effects require careful controls^[10][11].