PURPOSE: This review will address recent findings on apolipoprotein M (apoM) and its ligand sphingosine-1-phosphate (S1P) in lipid metabolism and inflammatory diseases.

RECENT FINDINGS: ApoM's likely role(s) in health and disease has become more diverse after the discovery that apoM functions as a chaperone for S1P. Hence, apoM has recently been implicated in lipid metabolism, diabetes and rheumatoid arthritis through in-vivo, in-vitro and genetic association studies. It remains to be established to which degree such associations with apoM can be attributed to its ability to bind S1P.

SUMMARY: The apoM/S1P axis and its implications in atherosclerosis and lipid metabolism have been thoroughly studied. Owing to the discovery of the apoM/S1P axis, the scope of apoM research has broadened. ApoM and S1P have been implicated in lipid metabolism, that is by modulating HDL particles. Also, the importance in regulating endothelial function is being investigated. Furthermore, both apoM and S1P have been linked to diabetes and glucose and insulin metabolism. Finally, genetic variations in the apoM gene are associated with lipid disturbances, diabetes and rheumatoid arthritis. These findings suggest not only diverse effects of apoM, but also the important question of whether apoM mainly acts as a S1P carrier, if apoM carries other substances with biological effects as well, or whether the apoM protein has effects on its own.