However, it is important to keep in mind that even in the endothelium S1P and its receptors elicit several potentially anti-atherogenic effects beyond the regulation of transendothelial lipoprotein transport,53 for example, on the transmigration of leucocytes and nitric oxide production.54 Therefore, and because of the cholesterol-lowering effects of both the S1P1 and the S1P3 knock-ins, we cannot conclude any causal link between reduced atherosclerosis and beneficially altered transendothelial lipoprotein transport. The gene discussed is S1PR1; the disease is atherosclerosis.