Thus, NA14 could conceivably play a role in cytokinesis by regulating the localization and the microtubule-severing activity of spastin at the midbodies. Of possible relevance, NA14 expression is upregulated in T-cell acute lymphoblastic leukemia characterized by an amplification of 9q34 and is differentially expressed in pancreatic cancer. Several groups have shown that spastin influences microtubule dynamics in growth cones, regulating the stability of axons and axonal transport. For example, Yu et al. showed that expression of spastin regulates axon length and number of branches. They further observed that the expression of spastin positively correlates with the formation of PF-04217903 c-Met inhibitor branches and the axon size. Based on our studies in neurons, it seems reasonable to postulate that NA14 might regulate spastin. Notably, NA14 is accumulated at the centrosome during the initiation of axon formation. Spastin and related proteins such as katanin have been implicated in releasing microtubules from the centrosome during mitosis, as well as in mechanisms that regulate microtubule length in axons of postmitotic neurons. Thus, we can imagine that NA14 might trigger spastin-dependent microtubulesevering in a specific cellular location at a specific time. Further studies of the NA14-spastin interaction in vitro and in cells will be necessary to test this hypothesis. Long axons of neurons within the corticospinal tract are highly dependent on spastin function. NA14 seems to play a role in neuronal development, in particular in axon outgrowth. The accumulation of NA14 could thus regulate the recruitment and/or regulation of spastin during the development of axons. In fact, previous studies have shown that spastin acts as a microtubulesevering protein in mammalian cells, and expression of spastin mutants unable to hydrolyze ATP result in the increased formation of stable bundles of microtubules. Moreover, Rodrı´guez-Rodrı´guez et al. have shown that NA14 can create a dynamic matrix between microtubules and spastin, providing a scaffold for anchoring proteins that are involved in microtubule nucleation and axonal development. A transport role for NA14 also has precedent, since NA14 has previously been implicated in transport of the orphan receptor TPRA40/GPR175, and the interaction with NA14 is required for the effects of TPRA40/GPR175 on cell division in mouse embryos. Lastly, NA14 was identified in a high-content screen for cilia genes as a protein involved in transport/trafficking of ciliary proteins. In conclusion, our findings suggest that NA14 is involved in cytokinesis and neuronal development. NA14 could regulate the localization and activity of the microtubule-severing AAA protein spastin in the midbody as well as during axon outgrowth. The involvement of NA14 in dynamic remodeling of the microtubule cytoskeleton, in developing and adult axons, and in the regulation of spastin serves a springboard to understanding the functional roles of their interaction.