S1PR4

S1PR4 is an S1P-responsive G-protein-coupled receptor that regulates cell shape and motility through Gαi and Gα12/13 coupling^[1]. In immune cells, S1PR4 transduces S1P effects on T-cell proliferation and cytokine secretion without signaling migration, distinguishing it from migration-dominant S1P receptor functions^[2]. Mechanistically, S1PR4 deficiency affects dendritic-cell function and Th17-cell differentiation in a murine model^[3]. S1PR4 is also required for plasmacytoid dendritic-cell differentiation, because S1PR4-deficient mice show reduced plasmacytoid dendritic-cell abundance across organs^[4]. In human plasmacytoid dendritic cells, S1PR4 signaling preserves ILT7 surface expression and limits TLR7/9-induced IFN-α production^[5]. In disease models, S1PR4 promotes nonalcoholic steatohepatitis by activating the NLRP3 inflammasome in hepatic macrophages^[6]. Compared with related isoforms, S1PR4 shows a functional profile centered on immune-cell activation, cytokine control, dendritic-cell biology, and inflammasome-linked macrophage responses rather than broad chemotactic signaling^[2][3][5][6]. For experimental applications, potent and selective S1P4 receptor agonists provide pharmacological tools to decipher S1P4 biological function and assess therapeutic utility^[7].