Certain conjugated bile acids (e.g., taurocholate, taurolithocholate) can act as agonists of S1PR2, especially when their circulating levels are elevated in cholestasis, leading to Rac1-dependent occludin phosphorylation and BBB leakiness. Thus, bile acid pool shifts toward conjugated, hydrophobic species in liver disease drive S1PR2-mediated barrier disruption and CNS inflammation [103,137,139]. Here, RAC1 is linked to cholestasis.