Syntrophin is an adaptor protein that binds signaling molecules to the dystrophin-associated protein complex, which connects extracellular matrix to intracellular cytoskeleton for construction and maintenance of the postsynaptic structures in the neuromuscular junction and the CNS. Among these signaling molecules, a family of microtubule-associated serine/threonine kinases has a unique structural feature with a serine/threonine kinase domain and a postsynaptic density protein-95/discs large/zona occludens-1 domain. In the present study, we identified syntrophin-associated serine/threonine kinase-124, a novel splice variant of the syntrophin-associated serine/threonine kinase which is a member of the microtubule-associated serine/threonine kinases family. Comparing to the original clone (syntrophin-associated serine/threonine kinase-170), syntrophin-associated serine/threonine kinase-124 is truncated just downstream of the postsynaptic density protein-95/discs large/zona occludens-1 domain. Using a monoclonal antibody specifically recognizing syntrophin-associated serine/threonine kinase-124, strong expression of the protein was observed in neurons of the subventricular zone and granule cells of the olfactory bulb, Islands of Calleja, hippocampal dentate gyrus and cerebellum. syntrophin-associated serine/threonine kinase-124 is selectively localized in the nuclei of neurons and distinct from syntrophin-associated serine/threonine kinase-170, which is interacting with syntrophin on the cell surface. Considering the tissue and subcellular distributions of syntrophin-associated serine/threonine kinase-124, it is suggested that syntrophin-associated serine/threonine kinase-124 may have functions in transcriptional regulation for the features commonly shared by these neurons. On the other hand, syntrophin-associated serine/threonine kinase-124 was also localized in glia-like cell bodies in the corpus callosum and fiber bundles in the spinal trigeminal and solitary tracts, suggesting syntrophin-associated serine/threonine kinase-124 may have other functions in these types of cells.