Once activated, HIPK2 phosphorylates the tumor suppressor p53 at serine 46 (Ser46) [20,29], the anti-apoptotic co-repressor CtBP [30], the p53 inhibitor MDM2 [31], or the pro-survival dominant negative isoform of the p53 family member p63 (ΔNp63α) [32], leading to cancer cell apoptosis (Figure 1). The gene discussed is HIPK2; the disease is cancer.