Growth Differentiation Factor 15 (GDF-15), also called Macrophage Inhibitory Cytokine 1 (MIC-1), is a divergent member of the TGF-beta superfamily. GDF15 can be secreted by a wide variety of cell types in response to a broad range of stressors. GDF-15 expression is dramatically upregulated during acute brain injury, cancer, cardiovascular disease, and inflammation, suggesting its potential value as a disease biomarker. GDF15 was shown to inhibit proliferation of primitive hematopoietic progenitors and introduced as a putative placental mediator of embryonic development. GDF15 has recently gained scientific and translational prominence with the discovery that its receptor is a GFRAL-RET heterodimer of which GFRAL is expressed solely in the hindbrain.