This suggests that IKAP may play a role in fine-tuning of the innervation process and the reading of environmental queues. In this respect we show that ikbkap downregulation directly affects growth cone morphology and probably axonal transport dependent signal transduction. We show that IKAP protein is colocalized with tubulin, dynein, and pJNK in the growth cones, while ikbkap downregulation leads to tubulin aggregation as can be judged by shifts in the fluorescence intensity and density patterns. These results indicate that IKAP is directly involved in tubulin organization in the growth cone, probably via its association with pJNK. Although IKAP ability to bind and regulate JNK activation in HEK-293 cells was described over a decade ago, here we show, for the first time, IKAP colocalization with pJNK at the growth cones in PNS neurons. This supports the view that IKAP could serve as a scaffold protein to facilitate known JNK dependent neuronal functions, such as axonal microtubule stabilization via phosphorylation of MAP1B, and microtubule plasticity via phosphorylation of superior cervical ganglion 10 protein in the growth cone. Interestingly, it was previously found that SCG10 is upregulated in FD cerebellum and fibroblasts, and in our ikbkap downregulated neuroblastoma model, possibly as part of the compensatory response to microtubule instability. In addition, JNK was found to phosphorylate kinesin 1 motor domain, which leads to dissociation of kinesin 1 from microtubules, BIBW2992 regulating axonal transport. Altogether, these observations support the view that IKAP is playing an essential role in the dynamics of microtubule reorganization and integration of signaling cues required for regulation of axonal outgrowth, branching, and gene expression in neurons. Concurrently, in this respect, we show for the first time that IKAP may be associated with dynein localization and may regulate in some way pJNK and NGF retrograde signaling in outgrowing neurons. We suggest that IKAP can play a role as a scaffold transport protein integrating extracellular signals by selective binding to specific signaling cargoes on one side and affinity binding to polymerizing microtubules in the growth cone at the other side. These diverse activities performed by IKAP allow specific transport of cargoes via dynein to the nucleus, regulating, in turn, the transcription of target genes, which contribute to many aspects of DRG neuronal function, including axon outgrowth and guidance, synapse maintenance, and cell survival. Supporting this hypothesis, we previously found in neuroblastoma gene expression microarray that IKAP deficiency induced the expression of several cytoskeleton and actinbinding proteins, while mostly, genes of axon guidance, axonal growth, and synapse structure and function where significantly downregulated, supporting IKAP role in neuronal outgrowth, guidance, and function. Specifically, axon guidance genes like Semaphorins, DPYSL3, Ret and other transmembrane receptor protein tyrosine kinases, NetrinG1 and other extracellular matrix proteins, TNR, TNC, and NAV2 were affected. Thus, in turn, the outgrowth and branching phenotypes observed here in ikbkap downregulated DRG neurons.