TSPAN18 (tetraspanin 18) is a transmembrane protein that functions as a critical regulator of store-operated calcium entry (SOCE) and inflammatory signaling. Its primary role involves facilitating cell surface localization of the calcium channel ORAI1 12. In endothelial cells, TSPAN18 interacts directly with ORAI1, and TSPAN18 knockdown reduces ORAI1 surface localization by 70%, impairing calcium mobilization upon inflammatory stimulation 1. This interaction enables von Willebrand factor (VWF) release in response to thrombin or histamine, with TSPAN18 knockdown reducing histamine-induced VWF release by 90% 1. Beyond endothelial function, TSPAN18 enhances bone metastasis in prostate cancer by protecting STIM1 (another SOCE component) from TRIM32-mediated ubiquitination, thereby stabilizing STIM1 protein and promoting calcium-dependent cell migration and invasion 3. Clinically, TSPAN18 overexpression correlates with poor prognosis in prostate cancer bone metastasis 3. Regarding psychiatric disease, while initial GWAS identified TSPAN18 variants as schizophrenia susceptibility loci in East Asian populations 45, subsequent replication studies in Han Chinese failed to confirm associations for most SNPs 67, suggesting population-specific effects. These findings position TSPAN18 as a therapeutic target for thrombo-inflammatory and metastatic diseases.