MLKL belongs to the protein kinase superfamily. The protein encoded by this gene contains a protein kinase-like domain; however, it is considered to lack protein kinase activity. This protein plays a crucial role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process, by interacting with receptor-interacting protein 3 (RIP3), which is a key signaling molecule in the necroptosis pathway. Upon phosphorylation and activation by RIPK3, it forms a homotrimer, localizes to the plasma membrane, and executes programmed necrosis, characterized by calcium influx and plasma membrane damage.
