Tetraspanin-18 (TSPAN18)

Tetraspanin-18 (TSPAN18) is a member of the tetraspanin superfamily of membrane proteins, characterized by four transmembrane domains. It is expressed at relatively high levels in endothelial cells and regulates the trafficking, surface localization, and clustering of the Ca²⁺ channel Orai1. Through this interaction, TSPAN18 controls store-operated calcium entry and is essential for von Willebrand factor release upon endothelial activation by inflammatory stimuli. Loss or inhibition of TSPAN18 impairs endothelial Ca²⁺ signaling, reduces release of pro-thrombotic mediators, and protects from thrombo-inflammatory diseases in mice models, but also predisposes to increased bleeding. TSPAN18 has potential as a selective therapeutic target for diseases driven by endothelial activation and thrombosis.

Other names

Tetraspanin-18TSPAN18Tspan-18TSPANUNQ3042/PRO9858

Theoretical: inhibition/modulation of TSPAN18 would reduce endothelial Ca²⁺ signaling and von Willebrand factor release, limiting thrombo-inflammatory response. By targeting the interaction with Orai1, selective modulation of store-operated Ca²⁺ entry could be achieved in endothelial cells.