The importance of the multi-domain interaction between IP3Rs and Bcl-2 is underpinned by the fact that peptides antagonizing Bcl-2 at its BH4 domain (like Bcl-2/IP3 Receptor Disrupter-2; BIRD-2) are able to trigger pro-apoptotic Ca2+ signaling in a variety of cancer-cell models, including lymphoma, leukemia and lung cancer cells [35, 37, 61]. This evidence concerns the gene BCL2 and cancer.