Mixed lineage kinase domain-like pseudokinase: Conventional (necroptosis) and unconventional (necroptosis-independent) functions and features

Abstract

Mixed lineage kinase domain-like pseudokinase (MLKL) is the terminal and indispensable mediator of necroptosis. Necroptosis, also known as programmed cell necrosis, is a caspase-independent cell death mechanism involved in various pathologic and inflammatory processes. Triggering necroptosis could be an alternative approach in treating apoptosis-resistant cancer cells to prevent recurrent disease. In addition to its function in necroptosis, MLKL plays a role as a regulator in many cellular processes independent of necroptosis. A better understanding of the intracellular function of MLKL and its role in various diseases and pathologic conditions is needed to enable discovery of new targeted therapies. Various necroptosis-dependent and independent functions of MLKL are reviewed in this chapter, with a focus on functions of MLKL in necroptosis, autophagy, inflammation, tissue regeneration, and endosomal trafficking.