Ergothioneine: Biosynthesis, Molecular Mechanisms, Physiological Function, and Role in Disease.

Ergothioneine (EGT) is a diet-derived sulfur-containing histidine derivative with antioxidant, anti-inflammatory, and cytoprotective properties. In humans, its absorption, tissue distribution, and long-term retention are mainly mediated by the organic cation transporter OCTN1, which may help explain its accumulation in metabolically active and stress-prone tissues. Increasing experimental and clinical evidence links EGT to neurodegenerative, cardiovascular, metabolic, inflammatory, and age-related disorders, although its therapeutic value still requires confirmation in larger and longer-term clinical studies. This review summarizes the physiological functions of EGT, its OCTN1-dependent transport and tissue distribution, and the molecular mechanisms by which it may modulate oxidative stress, inflammation, mitochondrial function, and cellular senescence. Particular attention is given to the dual role of the OCTN1/EGT axis in aging and tumor biology. In addition, we briefly discuss current biosynthetic and biomanufacturing strategies as practical tools for obtaining high-purity EGT for mechanistic, preclinical, and translational studies. By placing production strategies in the context of biomedical research needs, this review aims to provide a medically oriented overview of EGT biology and its potential translational applications.