Emerging roles of structural elements guiding human heme peroxidase function and interactions.

The human heme peroxidase family-comprising myeloperoxidase, eosinophil peroxidase, lactoperoxidase, thyroid peroxidase, and peroxidasin-shares a conserved catalytic core but exhibits diverse structural, functional, and pathophysiological profiles. While physiologically vital for innate immunity, hormone biosynthesis, and extracellular matrix remodelling, aberrant peroxidase activity drives severe conditions like chronic inflammation, autoimmunity, and cancer. Myeloperoxidase remains the only physiologically, biochemically and structurally well characterized human heme peroxidase. Significant knowledge gaps remain regarding the multi-domain enzymes thyroid peroxidase and peroxidasin. This review outlines structural determinants of enzyme reactivity and emphasizes the urgent need to elucidate native oligomeric states and broader interactomes to advance both biochemical understanding therapeutic drug discovery.