LEPROT (leptin receptor overlapping transcript) is a tetraspanning membrane protein that negatively regulates leptin receptor (LEPR) and growth hormone receptor (GHR) cell surface expression, thereby reducing cellular responsiveness to these hormones 1. LEPROT functions by controlling intracellular protein trafficking, decreasing receptor localization to the cell surface through endosomal and multivesicular body sorting pathways 12. During nutrient restriction, LEPROT expression increases via FGF21 signaling through FGFR1 and ERK1 pathways, promoting hepatic and skeletal growth plate GH resistance 2. This mechanism is physiologically significant: LEPROT and its paralog LEPROTL1 cooperatively suppress GH signaling during food scarcity, reducing IGF-1 levels and impairing growth 1. In humans, LEPROT expression correlates positively with insulin sensitivity and metabolic pathway upregulation in skeletal muscle and adipose tissue 3. Genetic association studies identify LEPROT as a candidate gene for growth-related traits in both livestock and humans, suggesting conserved metabolic regulation across mammalian species 4. Notably, LEPROT is located on human chromosome 1, overlapping with the LEPR gene locus 5. These findings indicate LEPROT serves as a molecular link between nutritional sensing and metabolic hormone signaling, with potential implications for understanding growth disorders and metabolic disease.