The article discusses the discovery and characterization of the leptin receptor, a key molecule in regulating body weight and energy balance. Initially, genetic obesity syndromes *ob* and *db* mice were identified, leading to the identification of the *ob* gene and its product, leptin, through positional cloning. Leptin is a hormone produced primarily by adipose tissue and acts as an "adipostat" to regulate appetite and metabolism. The *db* gene, which encodes the leptin receptor (OB-R), was later identified and found to be defective in *db* mice, leading to leptin resistance. The OB-R is a member of the class I cytokine receptor family and can activate signaling pathways involving JAK and STAT proteins. The article also highlights the importance of different forms of the OB-R, including the long and short forms, and their roles in signal transduction. The identification of the OB-R has opened up new avenues for understanding and treating obesity, particularly through the development of leptin receptor agonists.The article discusses the discovery and characterization of the leptin receptor, a key molecule in regulating body weight and energy balance. Initially, genetic obesity syndromes *ob* and *db* mice were identified, leading to the identification of the *ob* gene and its product, leptin, through positional cloning. Leptin is a hormone produced primarily by adipose tissue and acts as an "adipostat" to regulate appetite and metabolism. The *db* gene, which encodes the leptin receptor (OB-R), was later identified and found to be defective in *db* mice, leading to leptin resistance. The OB-R is a member of the class I cytokine receptor family and can activate signaling pathways involving JAK and STAT proteins. The article also highlights the importance of different forms of the OB-R, including the long and short forms, and their roles in signal transduction. The identification of the OB-R has opened up new avenues for understanding and treating obesity, particularly through the development of leptin receptor agonists.