Up to 3% of the world’s population suffers from obsessive-compulsive disorder (OCD), which has led to high costs in treatment and loss of work. Several hypotheses have been proposed to explain the development of OCD, but our current understanding is still limited, and today’s treatments are only partially effective. We are investigating the potential role of the neurotransmembrane protein, Slitrk5, which may be one of the missing pieces in our understanding of developing OCD. Recent studies have associated a deficient Slitrk5 with OCD. In our exploratory study, we utilized ultrastructural analysis with Serial-Block Face Scanning Electron Microscope (SBF-SEM) to identify and visualize ultrastructural alterations at nanometer resolution of the Slitrk5-/- mouse. The Slitrk5-/- is an OCD mouse model, where the Slitrk5 protein has been constitutively knocked out. We prepared 80 µm thick sections of tissue from the dorsal medial area of the striatum (DMS) of the Slitrk5-/- (n= 5, male) and wild type mice, C57BL/6 (n = 3, male) for the SBF-SEM. The outcome of the SBF-SEM was a series of images (Block of ~1000 40 nm thin sections) covering an area of approximately 30x30x30 μm in the DMS. Each block was rendered, visualized, and analyzed to uncover structural alterations of myelinated axons. The ultrastructural analysis revealed deformations and degenerations of myelinated axons in the tissue of the Slitrk5-/- mouse. The preliminary result suggests that experimental deletion of the Slitrk5 protein in mice leads to the development of abnormal myelin membrane extensions, myelin redundancy, and degenerations of myelinated axons within fiber bundles of the DMS. These findings highlight the previously unknown crucial role of the Slitrk5, as a structurally important synaptic-associated protein that has a crucial regulatory effect on myelinated axons, and that a deficiency of this protein leads to degenerative processes, at least in the DMS. Overall, these data support the hypothesis that Slitrk5 plays an essential role in the development of OCD-like phenotypes. We are currently conducting additional structural studies on the Slitrk5-/- mouse to further validate our findings. These include mesoscale analysis to 3D visualize the Cortico-Striatal Circuitry by retrograde labeling combined with whole-brain tissue clearing technique to map the entire long-range connectivity of the Cortico-Striatal Circuit. Additionally, we are performing macroscale structural analysis of the dorsal medial striatum, using multiplexing methods to examine ~30 different structural proteins to reveal molecular and cellular structural alterations within the DMS of the Slitrk5-/- mouse.