RIPK3

RIPK3 is a receptor-interacting serine/threonine kinase that drives necroptosis, a regulated inflammatory cell death pathway requiring RIPK3 and MLKL^[1]. Mechanistically, RIPK3 phosphorylates MLKL, enabling MLKL oligomerization, plasma membrane localization, and necrotic membrane disruption^[2][3]. In disease models, RIPK3-dependent necroptosis contributes to inflammatory injury, while RIPK3 also supports NLRP3 inflammasome activation through caspase-8 under IAP-deficient TLR signaling. Compared with RIPK1, RIPK3 shares RHIM-mediated necrosome signaling but lacks the same receptor-adaptor role; RIPK1 can both activate RIPK3 after receptor stimulation and suppress spontaneous RIPK3 activation in the cytosol^[4]. For experimental applications, RIPK3 inhibitors such as GSK′840, GSK′843, and GSK′872 bind the RIPK3 kinase domain and inhibit enzyme activity, but these compounds can also induce RIPK3-dependent apoptosis^[5]. - RIPK3 is central for studying necroptosis, MLKL phosphorylation, inflammatory signaling, and disease models. - RIPK3 inhibitors help dissect kinase-dependent signaling but require apoptosis controls in experimental design.