IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) is a human gene encoding the IKAP protein, which is ubiquitously expressed at varying levels in all tissue types, including brain cells. The IKAP protein is thought to participate as a sub-unit in the assembly of a six-protein putative human holo-Elongator complex, which allows for transcriptional elongation by RNA polymerase II. Further evidence has implicated the IKAP protein as being critical in neuronal development, and directs that decreased expression of IKAP in certain cell types is the molecular basis for the severe, neurodevelopmental disorder familial dysautonomia. Other pathways that have been connected to IKAP protein function in a variety of organisms include tRNA modification, cell motility, and cytosolic stress signalling. Homologs of the IKBKAP gene have been identified in multiple other Eukaryotic model organisms. Notable homologs include Elp1 in yeast, Ikbkap in mice, and D-elp1 in fruit flies. The fruit fly homolog (D-elp1) has RNA-dependent RNA polymerase activity and is involved in RNA interference. The IKBKAP gene is located on the long (q) arm of chromosome 9 at position 31, from base pair 108,709,355 to base pair 108,775,950. Function and mechanism Originally, it was proposed that the IKBKAP gene in humans was encoding a scaffolding protein (IKAP) for the IκB enzyme kinase (IKK) complex, which is involved in pro-inflammatory cytokine signal transduction in the NF-κB signalling pathway. However, this was subsequently disproven when researchers applied a gel filtration method and could not identify IKK complexes contained in fractions with IKAP, thus dissociating IKAP from having a role in the NF-κB signalling pathway. Later, it was discovered that IKAP functions as a cytoplasmic scaffold protein in the mammalian JNK-signalling pathway which is activated in response to stress stimuli. In an in vivo experiment, researchers showed direct interaction between IKAP and JNK induced by the application of stressors such as ultraviolet light and TNF-α (a pro-inflammatory cytokine). IKAP is now also widely acknowledged to have a role in transcriptional elongation in humans. The RNA polymerase II holoenzyme constitutes partly of a multi-subunit histone acetyltransferase element known as the RNA polymerase II elongator complex, of which IKAP is one subunit. The association of the elongator complex with RNA polymerase II holoenzyme is necessary for subsequent binding to nascent pre-mRNA of certain target genes, and thus their successful transcription. Specifically, within the cell, the depletion of functional elongater complexes due to