The leptin receptor (LEPR), a member of the cytokine receptor family, plays a pivotal role in regulating energy balance and appetite. Upon binding to its ligand leptin (LEP), LEPR activates multiple intracellular signaling pathways that generate a satiety signal. Rare genetic mutations that alter LEPR expression or structure are known to contribute to severe obesity and eating disorders. Our collaborators have identified are rare missense mutation of LEPR in a patient with morbid obesity. Conservation-based analyses and structural interpretation have highlighted the likely importance of this residue for overall stability, flexibility, and function of the receptor. It also seems that this mutation may have a profound dynamic effect on the overall behavior of the N-terminal domain. This project seeks to further investigate possible dynamic differences between the mutant and wild-type properties of the N-terminal domain of LEPR. In a larger context, these results may provide a better understanding of the involvement of the LEPR gene mutation in the development of obesity, which may be useful for future therapeutic approaches.