Apolipoprotein M (APOM) is a 26-kDa lipocalin family protein primarily expressed in hepatocytes and kidney tubule epithelial cells, predominantly associated with high-density lipoproteins (HDLs) in plasma 1. APOM functions as the primary chaperone for sphingosine-1-phosphate (S1P), a bioactive lipid critical for cellular signaling 2. Its hydrophobic binding pocket enables transport of multiple ligands including S1P, fatty acids, and retinoids 3. Mechanistically, APOM facilitates preβ-HDL formation and mediates atheroprotective HDL effects, including cholesterol efflux and reverse cholesterol transport 3. APOM expression is transcriptionally regulated by hepatocyte nuclear factors (HNF-1α, HNF-4α) and downregulated by nuclear receptors (LXR, RXR, FXR) and cytokines 1. Clinically, APOM shows relevance across multiple diseases: plasma APOM levels are reduced in diabetes and inversely correlate with glucose levels 3, altered in non-alcoholic fatty liver disease and cirrhosis 4, and dysregulated in hepatic fibrosis, viral hepatitis, and hepatocellular carcinoma via the apoM-S1P axis 5. APOM polymorphisms associate with lung function and emphysema severity in COPD 6. The apoM-S1P pathway represents a therapeutic target for autoimmune diseases, inflammatory conditions, and hepatic disorders 2, 7.