S1PR4 and Alzheimer disease: Our results, showing that GluN2B subunits are internalized through an endocytic process triggered by S1P signalling mainly via activation of S1P1 and S1P4 and, to a minor extent, S1P3 and S1P5, reinforce the great protective value of S1P against the abnormal activation of extrasynaptic NMDARs in the cytotoxic cascade responsible for neurodegeneration in AD.