Irisin, a myokine discovered in 2012, has emerged as a multifaceted hormone with far-reaching implications for human health and disease. Irisin's influence extends to metabolic regulation where it plays a crucial role in energy expenditure, glucose homeostasis and the browning of white adipose tissue. Named after the Greek messenger goddess Iris, Irisin serves as a molecular communicator, transmitting signals of physical activity and metabolic well-being throughout the body. Initially thought to primarily affect skeletal muscle physiology, intriguingly, Irisin is not solely the product of skeletal muscles but is secreted by various other tissues including adipose tissue, the brain and the liver. The central nervous system's regulation of irisin production has implications for neurodegenerative diseases, cognitive function and mood disorders. Additionally, we discuss the clinical applications and therapeutic potential associated with modulating irisin levels. Understanding the multifaceted role of irisin in health and disease has opened new avenues for interventions and therapies to enhance human well-being. This review provides a comprehensive overview of irisin's diverse roles, shedding light on its profound impact on health and disease. © 2025 Elsevier B.V., All rights reserved.