CLSTN1 (calsyntenin 1) is a neuronal cell adhesion protein that plays multiple roles in neural development, synaptic function, and disease pathogenesis. In neural development, CLSTN1 functions as part of the CTNNBIP1-CLSTN1 fusion transcript that regulates neural progenitor cell maintenance and differentiation through fine-tuning of Wnt/β-catenin signaling 1. This fusion transcript is essential for proper human neocortical and retinal development, preventing precocious neuronal differentiation 12. At the cellular level, CLSTN1 localizes to plasma membranes, intracellular vesicular structures, and cell-cell contact regions where it mediates cell adhesion and potentially synaptic signaling 3. The protein's expression and localization are regulated by MAP4 kinases, which suppress CLSTN1 recruitment to cell-cell contacts 3. In disease contexts, CLSTN1 exhibits tumor-suppressive properties, as reduced expression increases invasiveness in medulloblastoma 3. Alternative splicing of CLSTN1 is crucial for epithelial-mesenchymal transition regulation in breast cancer metastasis 4. Additionally, CLSTN1 shows potential as a therapeutic target, being associated with type 2 diabetes mellitus risk and involved in neuroprotection through S-nitrosation mechanisms in ischemic stroke 56. CLSTN1 expression is also altered in trigeminal neuralgia and regulated by DNA methylation in obesity-associated immune cells 78.