TANK was initially identified as a novel TRAF-interacting protein that regulated TRAF-mediated signal transduction. Specifically, ligand binding by surface receptors in the tumor necrosis factor (TNF) receptor and Toll/interleukin-1 (IL-1) receptor families lead to the formation of a TRAF/TANK complex that mediates the activation of the transcription factor NF-κB. This activation of NF-κB occurs through an association with the kinases IKKε and TBK1. More recently, it was shown that these proteins can then form a complex with NEMO, a protein that regulates the activity of the IκB complex. This suggests that in addition to the possibility that TBK1 and IKKε activate the IKKs, the association with the IKK complex may help these kinases modulate other functions, such as the transactivation potential of NF-κB proteins. At least two isoforms of TANK are known to exist.