{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMyoglobin (MB) is best known as a heme‐containing globular protein predominantly expressed in cardiac and oxidative skeletal muscle where it serves as an intracellular reservoir and facilitator of oxygen supply. Its classical functions include the storage of O₂ and its intracellular diffusion to mitochondria under conditions of high metabolic demand and low perfusion, as well as the regulation of nitric oxide bioactivity. Detailed kinetic and structural studies have delineated key features of its ligand‐binding dynamics—such as the conformational “gate” governed by the distal His residue—that allow efficient oxygen and NO handling. In addition, investigations into apomyoglobin folding and aggregation have further underscored the delicate structural balance necessary for its optimal function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its essential physiological role in oxygen handling, MB has emerged as an invaluable diagnostic biomarker in clinical practice. Its circulating levels are measured in rapid, ultrasensitive assays designed for early detection of acute myocardial infarction, rhabdomyolysis, and related kidney injury, while alterations in plasma MB also correlate with muscle mass and fiber‐type composition in settings such as cancer‐associated cachexia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have broadened our understanding of MB by revealing its expression outside of traditional muscle tissue. MB is now known to be ectopically expressed in a range of epithelial tumors—including breast, lung, prostate, and renal carcinomas—where its induction by hypoxia and modulation by hormonal factors appear to influence cellular energy metabolism, reactive oxygen species handling, and proliferative as well as migratory behaviors. In these non‐muscle contexts, MB may function in a tumor‐suppressive capacity by tempering mitochondrial activity and oxidative stress, while specific transcript variants or epigenetic regulatory networks further tailor its expression. Moreover, rare, pathogenic MB mutations have been linked to a progressive myopathy characterized by sarcoplasmic inclusions, underscoring how critical the integrity of MB’s structure and function is for cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paul Robach, Gaetano Cairo, Cecilia Gelfi, et al. 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