LEAP2 (liver enriched antimicrobial peptide 2) is a hormone primarily produced by hepatocytes and enterocytes that functions as an endogenous antagonist and inverse agonist of the ghrelin receptor (GHSR) 1. Originally identified as an antimicrobial peptide, LEAP2 has emerged as a key regulator of energy homeostasis by suppressing appetite and food intake in both rodents and humans 23. The peptide counters ghrelin's orexigenic effects and modulates growth hormone secretion through GHSR binding 4. LEAP2 exhibits unique regulatory features, being found in higher plasma concentrations than ghrelin even during energy deficit states and modulating both ghrelin-dependent and ghrelin-independent GHSR activities 4. Mechanistically, LEAP2 is regulated by insulin and glucagon, with glucagon infusions decreasing plasma LEAP2 levels while insulin supports its postprandial upregulation 5. Clinically, LEAP2 shows promise as a therapeutic target for obesity and cardiometabolic disorders, with elevated serum levels correlating with increased BMI and metabolic dysfunction 13. The peptide's dysregulation has been implicated in polycystic ovary syndrome and chr5 kidney disease, suggesting broader metabolic significance 67.