In this review, we systematically summarized the roles of FNDC5/irisin in fat, liver, nerve, bone, skeletal muscle, articular cartilage, cancer, and angiocarpy. Irisin, as a muscle factor secreted by exercise, plays an extremely important role in regulating fat browning, improving liver and systemic glucose metabolism, maintaining musculoskeletal homeostasis, promoting synaptic growth, and inhibiting the progression of cancer. The mechanism of irisin is mainly through first directly binding to its receptor integrin αV/β1/5 and then activating AMPK, FAK, and MAPK signaling pathways. The gene discussed is FNDC5; the disease is cancer.