BIRC3 mutations are found in a smaller proportion of CLL patients (~4%) but they impact upon the non-canonical NF-κB pathway due to the premature truncation of the BIRC3-encoded protein product, cIAP2, resulting in the loss of its E3 ubiquitin ligase activity that is essential for NIK proteasomal degradation. Here, BIRC3 is linked to B-cell chronic lymphocytic leukemia.