Mixed lineage kinase domain-like protein (MLKL) (MLKL)

Mixed lineage kinase domain-like protein (MLKL) is a pseudokinase that serves as the essential executioner of necroptosis, a form of regulated inflammatory cell death. Upon activation by the upstream kinase RIPK3, MLKL is phosphorylated at specific residues (Ser358 and Thr357 in humans), which triggers a conformational change and its subsequent oligomerization. These oligomers translocate to the plasma membrane, where they disrupt membrane integrity, leading to cell lysis and the release of damage-associated molecular patterns (DAMPs). MLKL is a significant therapeutic target in inflammatory diseases, such as acute kidney injury and neurodegeneration, as well as in various cancers where necroptosis is either suppressed or contributes to a pro-tumorigenic environment. While the term P-MLK1 is frequently used in some literature to refer to the phosphorylated form of MLKL, it is technically a misnomer, as MLK1 (MAP3K9) is a distinct member of the MAP kinase kinase kinase family.

Other names

MLKLp-MLKLP-MLK1p-MLK1Mixed lineage kinase domain-like

Inhibition of MLKL oligomerization and membrane translocation to block necroptotic cell death.