Ceramide-mediated formation and action of MRRSPs. In response to various stimuli such as death receptor activation, lysosomes are mobilized to move and fuse to the cell membrane, where aSMase from lysosomes is activated to produce ceramide leading to MR clustering. During MR clustering, Nox subunits or related cofactors are aggregated and thereby assembled to form MRRSPs producing O2.−, conducting transmembrane signals. MRRSP-mediated ROS production has been shown to contribute to NLRP3 inflammasome activation, which serves as intracellular machinery to turn on the inflammatory response in many different cells. GDP, guanosine diphosphate; GTP, guanosine triphosphate; MR, membrane raft; MRRSP, membrane raft redox signaling platform; NADPH, nicotinamide adenine dinucleotide phosphate; NLRP3, NLR family pyrin domain containing 3; Nox, NADPH oxidase. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars