GDF15 and neoplasm: Based on the initial observation that tumor-derived GDF-15 induces this condition (35), on the localization of the underlying signaling mechanism to the brainstem (131), and on the identification of the brainstem-restricted GDF-15 receptor GFRAL and its signaling pathway via RET (28–30, 41), GDF-15 and GFRAL have become major targets for appetite and weight regulation.