A20, encoded by TNFAIP3, is a molecular “brake” of the canonical NF-κB activation pathway and attenuates the NF-κB activity triggered by a number of surface receptors.1,2 A20 contains an N-terminal OTU domain that possesses deubiquitinating activity, and 7 zinc finger (ZF) domains in its C-terminus that confers the E3 ubiquitin ligase activity.3 Through removing the K63-linked ubiquitin chain, catalysing the K48-linked polyubiquitination, and also direct binding to the linear polyubiquitin chain of its targets, A20 can inactivate a number of NF-κB positive regulators, including RIP1/2, TRAF6, Ubc13 and NEMO, thus negatively regulating the signalling of several surface receptors, including BCR, TNFR, TLR and IL1βR.1,2,4 A20 itself is a transcriptional target of NF-κB, and its transcriptional activation by NF-κB thus serves as an auto-negative feedback to attenuate NF-κB activities triggered by these receptor signallings.1,2