The relevance of endothelial derived S1P for hypertension has recently been addressed in greater detail by analyses using endothelial-cell specific Spns2-KO (ECKO-Spns2) mice to investigate the consequence of impaired S1P-secretion from ECs on endothelial dysfunction (Del Gaudio et al., 2021; Figure 2). This evidence concerns the gene SPNS2 and endothelial dysfunction.