The study by Fichtner et al. (2023) re-evaluates the expression pattern of the glial cell-derived neurotrophic factor receptor alpha-like (GFRAL) in the brain and peripheral tissues of mice. Previous research had identified GFRAL as a receptor for growth differentiation factor 15 (GDF15) exclusively in the brainstem area postrema (AP) and nucleus tractus solitarii (NTS), where it mediates GDF15's effects on reducing food intake and body weight. However, this study found that GFRAL is more widely distributed in the brain and peripheral tissues. Immunohistochemical analysis revealed GFRAL immunoreactivity in the prefrontal cortex, hippocampus, nucleus arcuatus, and peripheral tissues such as the liver, small intestine, fat, kidney, and muscle. This widespread expression suggests that GDF15 may have multiple effects beyond those previously attributed to GFRAL in the AP/NTS. The findings have implications for understanding and potentially treating disorders related to food intake, body image, and weight, such as eating disorders, cachexia, and obesity. The study also highlights the need for further research to understand the role of GFRAL in these conditions and to explore its potential as a therapeutic target.The study by Fichtner et al. (2023) re-evaluates the expression pattern of the glial cell-derived neurotrophic factor receptor alpha-like (GFRAL) in the brain and peripheral tissues of mice. Previous research had identified GFRAL as a receptor for growth differentiation factor 15 (GDF15) exclusively in the brainstem area postrema (AP) and nucleus tractus solitarii (NTS), where it mediates GDF15's effects on reducing food intake and body weight. However, this study found that GFRAL is more widely distributed in the brain and peripheral tissues. Immunohistochemical analysis revealed GFRAL immunoreactivity in the prefrontal cortex, hippocampus, nucleus arcuatus, and peripheral tissues such as the liver, small intestine, fat, kidney, and muscle. This widespread expression suggests that GDF15 may have multiple effects beyond those previously attributed to GFRAL in the AP/NTS. The findings have implications for understanding and potentially treating disorders related to food intake, body image, and weight, such as eating disorders, cachexia, and obesity. The study also highlights the need for further research to understand the role of GFRAL in these conditions and to explore its potential as a therapeutic target.