S-Geranylgeranyl-L-glutathione acts as a ligand for the orphan G protein-coupled receptor (GPCR) P2RY8, displaying selective affinity by inducing internalization of P2RY8 in preference to the sphingosine-1-phosphate receptor 2 (S1P2), GPR55, cysteinyl leukotriene receptor 1 (CysLT1 receptor), and the CysLT2 receptor at a concentration of 100 nM. Additionally, at a lower concentration of 10 nM, S-Geranylgeranyl-L-glutathione inhibits the chemokine (C-X-C motif) ligand 12-induced migration of both P2RY8-expressing WEHI-231 B cell lymphoma cells and human tonsil germinal center B cells.