LSP1 also activates the RIPK3-MLKL signaling axis, promoting MLKL phosphorylation and translocation to the cell membrane, thereby inducing necroptosis and releasing damage-associated molecular patterns such as HMGB1, which further activates innate immune cells and reshapes the tumor microenvironment (37, 44). This evidence concerns the gene HMGB1 and neoplasm.