Irisin, first identified as a protein encoded downstream of the transcriptional peroxisome proliferator-activated receptor gamma (PPAR-γ) co-activator-1 α (PGC1-α), has become almost ubiquitous with muscle physiology, obesity, metabolic syndrome, and diabetes, as well as neurodegenerative diseases. The gene discussed is FNDC5; the disease is obesity due to melanocortin 4 receptor deficiency.