MLKL

MLKL, short for Mixed Lineage Kinase Domain-Like Protein, is a key effector of necroptosis. Activated by RIPK3-mediated phosphorylation, it forms oligomers that translocate to the plasma membrane, disrupting lipid bilayers and inducing necrotic cell death. It functions in the RIPK1-RIPK3-MLKL signaling pathway, a core cascade for programmed necrosis.
Dysregulated MLKL activity links to inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease) and cancers. Drug development focuses on inhibitors targeting MLKL oligomerization or membrane translocation; preclinical candidates show efficacy in reducing necroptosis-related tissue damage, though no FDA-approved agents exist yet.