The BH3-only protein PUMA plays an essential role in p53-dependent and -independent apoptosis in human cancer cells and mice [13], and activates the mitochondrial pathway via the Bcl-2 family member Bax/Bak following neutralizing all members of antiapoptotic Bcl-2 like molecules [14], [15], [16], [17]. The gene discussed is BCL2; the disease is cancer.