Programmed cell death is a basic cellular process that is critical to 
maintaining tissue homeostasis. In contrast to apoptosis, necrosis was 
previously regarded as an unregulated and uncontrollable process. However, as 
research has progressed, necrosis, also known as necroptosis or programmed 
necrosis, is drawing increasing attention, not least becasu of its possible 
impications for cancer research. Necroptosis exhibits a unique signaling pathway 
that requires the involvement of receptor interaction protein kinases 1 and 3 
(RIP1 and RIP3), mixed lineage kinase domain-like (MLKL), and phosphoglycerate 
mutase 5 (PGAM5) and can be specifically inhibited by necrostatins. Not only 
does necroptosis serve as a backup cell death program when apoptosis is 
inhibited, but it is now recognized to play a pivotal role in regulating various 
physiological processes and the pathogenesis of a variety of human diseases such 
as ischemic brain injury, immune system disorders and cancer. The control of 
necroptosis by various defined trigger factors and signaling pathways now offers 
the opportunity to target this cellular process for therapeutic purposes. The 
purpose of this paper is to review current findings concerning the connections 
between various trigger factors and the RIP1/RIP3 signaling pathway as it 
relates to necroptosis.