Prior cellular metabolic studies recognized glial cell-derived neurotrophic factor family receptor-like (GFRAL), an orphan receptor in the GDNF family, as the GDF 15 receptor [36,37,38,39]; thereafter, evidences suggesting GDF15/GFRAL/RET (ret proto-oncogene signaling) is a target for treatment of metabolic diseases. The gene discussed is GDF15; the disease is metabolic disease.