GDF15 and obesity due to melanocortin 4 receptor deficiency: 44, 70 GDF-15 and GFRAL signaling pathways are thus suggested to be an important potential therapeutic target for both cancer cachexia and obesity.7, 16, 42, 46, 54, 71 Thus, both GDF15 and GFRAL signaling through the tyrosine kinase receptor RET18, 46 are under investigation in several clinical trials.43, 46 (Table 1)