S1PR2

S1PR2 is a sphingosine-1-phosphate receptor that mediates immune cell trafficking, angiogenesis, and vascular function through the S1P receptor family^[1]. Mechanistically, S1PR2 activates Rho-ROCK and PTEN signaling, disrupts adherens junctions, stimulates stress fibers, and increases endothelial paracellular permeability^[2]. In CNS autoimmunity models, increased S1PR2 expression destabilizes blood-brain barrier adherens junctions, while pharmacological blockade or genetic loss reduces EAE severity by improving endothelial barrier function^[3]. In germinal centers, S1P2/S1PR2 inhibits Akt activation and migration, thereby restricting B-cell survival and localization within an S1P-low follicular niche^[4]. Compared with related isoforms, S1PR2 contrasts with S1PR1-dependent endothelial barrier enhancement and with S1PR1/S1PR3 activation by S1P in receptor-internalization assays^[2][5]. For experimental applications, JTE-013 has been used as an S1PR2 antagonist, whereas CYM-5478 activates S1PR2 selectively and reduces cisplatin-mediated cell death by lowering ROS in neural-derived cell assays^[5][6].