Next to its role in suppressing NF-κB activation, A20 is also a strong inhibitor of apoptosis, at least in some cell types. The mechanisms by which A20 regulates apoptotic signalling, however, are still elusive. A20-deficient mice spontaneously develop multiorgan inflammation and cachexia and die within 2 weeks of birth, illustrating the potent anti-inflammatory function of this molecule [46]. A20-deficient cells are also more susceptible to TNF-mediated apoptosis, confirming its role as an antiapoptotic protein. We recently showed that mice specifically lacking A20 in intestinal epithelial cells exhibit increased susceptibility to experimental colitis due to the hypersensitivity of their intestinal epithelial cells to TNF-induced apoptosis, confirming A20 as a major antiapoptotic protein in the intestinal epithelium [47]. Two independent studies showed that mice lacking A20 in B cells develop autoimmunity due to hyperactive NF-κB responses in B cells leading to unrestricted B-cell survival [48,49].