This study reveals that the GFRAL receptor, previously thought to be exclusively expressed in the brainstem area postrema (AP) and nucleus tractus solitarii (NTS) of mice, is actually widely distributed in both the brain and peripheral tissues. Using immunohistochemical analysis, the researchers found GFRAL-immunoreactivity (IR) in various brain regions, including the prefrontal cortex, hippocampus, nucleus arcuatus, and peripheral tissues such as the liver, small intestine, fat, kidney, and muscle. This broader expression pattern suggests that GFRAL may be involved in multiple physiological processes beyond its previously described role in regulating food intake and body weight through the AP/NTS. GDF15, a cytokine with widespread expression and pleiotropic effects, binds specifically to GFRAL. The findings indicate that GFRAL's broader expression could explain the diverse effects of GDF15, which have not yet been fully attributed to GFRAL. The study also highlights the potential of the GDF15/GFRAL/RET signaling pathway as a therapeutic target for disorders related to body image and food intake, such as eating disorders, cachexia, and obesity. The research used immunofluorescence labeling and confocal microscopy to visualize GFRAL expression in various tissues. The results show that GFRAL is present in the brainstem, prefrontal cortex, hippocampus, and peripheral tissues, suggesting a more complex role for GFRAL in physiological processes than previously understood. The study also validates the use of a specific antibody for GFRAL detection and confirms its presence in human tissues, including gastric mucosa and pancreatic cells. The findings challenge the notion that GDF15's effects are limited to the AP/NTS and suggest that GFRAL may be activated in other brain areas and peripheral tissues via local or circulating GDF15. This broader expression of GFRAL could have implications for understanding and treating disorders related to body image and food intake. The study also highlights the need for further research into the role of GFRAL in disease conditions and the potential for developing novel pharmacological therapies targeting the GDF15/GFRAL pathway.This study reveals that the GFRAL receptor, previously thought to be exclusively expressed in the brainstem area postrema (AP) and nucleus tractus solitarii (NTS) of mice, is actually widely distributed in both the brain and peripheral tissues. Using immunohistochemical analysis, the researchers found GFRAL-immunoreactivity (IR) in various brain regions, including the prefrontal cortex, hippocampus, nucleus arcuatus, and peripheral tissues such as the liver, small intestine, fat, kidney, and muscle. This broader expression pattern suggests that GFRAL may be involved in multiple physiological processes beyond its previously described role in regulating food intake and body weight through the AP/NTS. GDF15, a cytokine with widespread expression and pleiotropic effects, binds specifically to GFRAL. The findings indicate that GFRAL's broader expression could explain the diverse effects of GDF15, which have not yet been fully attributed to GFRAL. The study also highlights the potential of the GDF15/GFRAL/RET signaling pathway as a therapeutic target for disorders related to body image and food intake, such as eating disorders, cachexia, and obesity. The research used immunofluorescence labeling and confocal microscopy to visualize GFRAL expression in various tissues. The results show that GFRAL is present in the brainstem, prefrontal cortex, hippocampus, and peripheral tissues, suggesting a more complex role for GFRAL in physiological processes than previously understood. The study also validates the use of a specific antibody for GFRAL detection and confirms its presence in human tissues, including gastric mucosa and pancreatic cells. The findings challenge the notion that GDF15's effects are limited to the AP/NTS and suggest that GFRAL may be activated in other brain areas and peripheral tissues via local or circulating GDF15. This broader expression of GFRAL could have implications for understanding and treating disorders related to body image and food intake. The study also highlights the need for further research into the role of GFRAL in disease conditions and the potential for developing novel pharmacological therapies targeting the GDF15/GFRAL pathway.