ABSTRACT: Calcium/calmodulin-dependent protein kinase 4 (gene and transcript: CaMK4; protein: CaMKIV) is the nuclear effector of the Ca/calmodulin kinase (CaMK) pathway where it coordinates transcriptional responses. However, CaMKIV is present in the cytoplasm and axons of subpopulations of neurons, including some sensory neurons of the dorsal root ganglia (DRG), suggesting an extranuclear role for this protein. We observed that CaMKIV was expressed strongly in the cytoplasm and axons of a subpopulation of small-diameter DRG neurons, most likely cutaneous nociceptors by virtue of their binding the isolectin IB4. In IB4+ spinal nerve axons, 20% of CaMKIV was colocalized with the endocytic marker Rab7 in axons that highly expressed CAM-kinase-kinase (CAMKK), an upstream activator of CaMKIV, suggesting a role for CaMKIV in signaling though signaling endosomes. Using fluorescent in situ hybridization (FISH) with riboprobes, we also observed that small-diameter neurons expressed high levels of a novel 3′ untranslated region (UTR) variant of CaMK4 mRNA. Using rapid amplification of cDNA ends (RACE), reverse-transcription polymerase chain reaction (RT-PCR) with gene-specific primers, and cDNA sequencing analyses we determined that the novel transcript contains an additional 10 kb beyond the annotated gene terminus to a highly conserved alternate polyadenylation site. Quantitative PCR (qPCR) analyses of fluorescent-activated cell sorted (FACS) DRG neurons confirmed that this 3′-UTR-extended variant was preferentially expressed in IB4-binding neurons. Computational analyses of the 3′-UTR sequence predict that UTR-extension introduces consensus sites for RNA-binding proteins (RBPs) including the embryonic lethal abnormal vision (ELAV)/Hu family proteins. We consider the possible implications of axonal CaMKIV in the context of the unique properties of IB4-binding DRG neurons. J. Comp. Neurol. 522:308–336, 2014. © 2013 Wiley Periodicals, Inc. : Sensory neurons of the DRG which bind the lectin IB4 are small-diameter, give rise to unmyelinated axons, and are generally cutaneous nociceptors. Using highly specific antibodies, we have demonstrated that CaMKIV is highly expressed in the cytoplasm and in axons arising from this IB4-binding population. In addition we have characterised a novel 3′ untranslated region (UTR)-extended transcript variant of this gene whose expression highly correlates with non-nuclear CaMKIV protein localization and IB4-binding. Possible mechanisms for, and functions of, axonally localised CaMKIV (a protein known for its function in the nucleus) in IB4-binding sensory neurons are discussed.(Figure is included in full-text article.)