GDF15 is a stress-responsive cytokine and member of the TGFβ superfamily that functions as a hormonal messenger conveying information about cellular stresses to the brain 1. It binds to its brainstem receptor GFRAL, activating neurons in the area postrema and nucleus tractus solitarius, which triggers an aversive response characterized by nausea, vomiting, and appetite suppression 2. This response serves dual functions: immediately reducing exposure to harmful stressors and promoting future avoidance behavior 1. GDF15 suppresses appetite and promotes weight loss through GFRAL-RET signaling independent of classical appetite hormones like leptin or ghrelin 1. Its expression is elevated by metformin, ketogenic diets, and exercise, making it a key mediator of metabolic interventions 3. GDF15 also regulates energy expenditure and adipose tissue metabolism, contributing to improvements in obesity and cardiometabolic diseases 4. Clinically, elevated GDF15 is associated with cancer cachexia, chemotherapy-induced anorexia, and hyperemesis gravidarum, where high fetal-derived GDF15 levels during pregnancy correlate with increased nausea and vomiting 2. In hepatocellular carcinoma, GDF15 promotes immunosuppression by expanding regulatory T cells through CD48 signaling 5. Additionally, GDF15 serves protective roles during aging and systemic stress, suggesting context-dependent pleiotropy 6.