K13. Taken collectively, the above results support the model according to which binding of K13 to NEMO manipulates the latter into an open conformation that facilitates the recruitment of IKK1 and IKK2 and their subsequent activation by ‘‘T loop’’ phosphorylation. Specific inhibitors of IKK (particularly IKK2) that can selectivity block NF-kB pathway are being developed by several pharmaceutical companies [68]. However, since the NF-kB pathway plays a key role in normal immune response [69], the clinical utility of such agents in KSHV-associated lymphoproli- ferative disorders is likely to be limited by their potential toxicity. For example, in vivo administration of ML120B, a small molecule selective inhibitor of IKK2, led to rapid depletion of T and B cells [70]. Although no IKK1-selective inhibitor has been described to date, genetic studies suggest that IKK1 may similarly play an essential role in lymphocyte development and function [71]. 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