In human glioblastoma, the A20 Znf domain mediates K63-linked polyubiquitination of RIP1 and thus inhibits cell death.26 The N-terminal ovarian tumor domain of A20 acts as a DUB by removing K63-linked polyubiquitin chains from RIP1, which consequently downregulates TNFα-induced NF-κB signaling.25 As discussed above, the role of A20 is much more complicated than that of an individual DUB or E3 ligase for its two opposite-function domains. The gene discussed is ZUP1; the disease is glioblastoma.