Rapamycin across biology and medicine: From molecular mechanisms to clinical and translational frontiers

Rapamycin is a macrolide compound originally identified for its antifungal activity and subsequently recognized as a potent inhibitor of the mechanistic target of rapamycin (mTOR), a conserved signaling kinase that integrates nutrient availability, growth factor signals, and cellular stress responses to regulate cell growth and metabolism. This review examines rapamycin across biological and medical fields, covering its discovery, chemical and pharmacological properties, and the central role of mTOR as its primary molecular target. We summarize established and emerging clinical applications of rapamycin and its analogs, while critically addressing the limitations and adverse effects associated with mTOR inhibition. Furthermore, advances in translational research and future perspectives are also discussed. Collectively, current evidence supports mTOR inhibition as a unifying biological strategy for the prevention, treatment, and delayed onset of multiple chronic diseases, as well as for promoting healthspan. As the first clinically approved mTOR inhibitor, rapamycin has therefore become a foundational pharmacological tool for exploring the therapeutic potential of modulating the evolutionarily conserved mTOR signaling network across a broad spectrum of human diseases and age-related conditions.