Leptin, an adipose tissue-derived hormone, plays a crucial role in maintaining homeostatic control of energy balance by regulating appetite and metabolism. While leptin inhibits orexigenic agouti-related protein (AGRP) neurons and activates anorexigenic pro-opiomelanocortin (POMC) neurons, the acute activation of POMC neurons has minimal effects on food intake. This has led to the discovery of a new population of leptin-responsive neurons in the arcuate nucleus (ARC) that rapidly suppresses appetite by directly inhibiting AGRP neurons. These neurons, identified as expressing basonuculin 2 (BNC2), are activated by leptin and sensory food cues, and their activity is modulated by nutritional status. Activating BNC2 neurons reduces food intake and body weight, while silencing them increases food consumption. Deletion of leptin receptors in BNC2 neurons causes hyperphagia and obesity, similar to AGRP neuron knockout. These findings highlight the importance of BNC2 neurons in the neural circuitry that maintains energy balance and provide new insights into the regulation of food intake by leptin.Leptin, an adipose tissue-derived hormone, plays a crucial role in maintaining homeostatic control of energy balance by regulating appetite and metabolism. While leptin inhibits orexigenic agouti-related protein (AGRP) neurons and activates anorexigenic pro-opiomelanocortin (POMC) neurons, the acute activation of POMC neurons has minimal effects on food intake. This has led to the discovery of a new population of leptin-responsive neurons in the arcuate nucleus (ARC) that rapidly suppresses appetite by directly inhibiting AGRP neurons. These neurons, identified as expressing basonuculin 2 (BNC2), are activated by leptin and sensory food cues, and their activity is modulated by nutritional status. Activating BNC2 neurons reduces food intake and body weight, while silencing them increases food consumption. Deletion of leptin receptors in BNC2 neurons causes hyperphagia and obesity, similar to AGRP neuron knockout. These findings highlight the importance of BNC2 neurons in the neural circuitry that maintains energy balance and provide new insights into the regulation of food intake by leptin.