METRNL (meteorin-like) is a secreted cytokine/myokine with pleiotropic immunometabolic functions. Primarily, METRNL is induced by exercise in skeletal muscle or cold exposure in adipose tissue and circulates systemically to promote energy expenditure and glucose homeostasis 1. Mechanistically, METRNL does not directly act on adipocytes but instead stimulates immune cell infiltration into adipose tissue, promoting eosinophil-dependent IL-4 expression and alternative macrophage activation to drive brown fat thermogenesis 1. METRNL signals via the KIT receptor tyrosine kinase on multiple cell types, including endothelial cells and immune cells 23. In disease contexts, METRNL demonstrates broad protective functions. In atopic dermatitis, METRNL enhances β-Catenin signaling to suppress Th2 inflammation and immune cell accumulation 3. In diabetic kidney disease, METRNL alleviates lipid accumulation through Sirt3-AMPK-mediated mitochondrial homeostasis 4. Following myocardial infarction, METRNL promotes angiogenesis and tissue repair via KIT-dependent endothelial expansion 2. The endothelium represents the major source of circulating METRNL (~75%), maintaining endothelial function and vascular homeostasis against atherosclerosis 5. Conversely, METRNL impairs anti-tumor CD8+ T cell metabolism by increasing mitochondrial depolarization and glycolytic dependency 6. These diverse functions position METRNL as a promising therapeutic target and biomarker for metabolic, cardiovascular, and inflammatory diseases 7.