Additionally, the availability of cell lines expressing RIPK3 is limited because RIPK3 is often silenced through DNA methylation in most cancer cells and tumor tissues.[12] To address these limitations, RIPK3 overexpression is often used, but this causes the autophosphorylation and subsequent activation of MLKL, indicating that this approach is insufficient for fully elucidating the complex dynamics of the pathway.[13] Thus, methods that can bypass these complex upstream interactions and directly activate the core effectors of necroptosis are clearly needed. The gene discussed is RIPK3; the disease is cancer.