While data from mouse models indicate that mice lacking S1PR1 develop severe thrombocytopenia caused by both the formation of aberrant extravascular proplatelets (PPs) and defective intravascular PP shedding [52], other groups more recently found that S1P may restrict megakaryopoiesis through S1PR1 and may further suppress thrombopoiesis through S1PR2 when aberrantly secreted in the hematopoietic niche [53]. The gene discussed is S1PR1; the disease is Thrombocytopenia.