This gene belongs to the protein kinase superfamily. The encoded protein contains a protein kinase-like domain; however, is thought to be inactive because it lacks several residues required for activity. This protein plays a critical role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process, via interaction with receptor-interacting protein 3 (RIP3), which is a key signaling molecule in necroptosis pathway. Inhibitor studies and knockdown of this gene inhibited TNF-induced necrosis. High levels of this protein and RIP3 are associated with inflammatory bowel disease in children. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Sep 2015]
Forensic Context
A study in mice demonstrated that hypothermia exposure induced necroptosis in cerebral cortical neurons, with protein levels of the MLKL significantly increased in the hypothermia-exposed cerebral cortex [Wang et al. DOI:10.1186/s11658-025-00772-0].