MPST (mercaptopyruvate sulfurtransferase) is a mitochondrial enzyme that catalyzes sulfur transfer reactions essential for hydrogen sulfide (H2S) biosynthesis and protein persulfidation. Its primary function involves transferring sulfur to cyanide and thiol compounds, with particular importance in the H2S-producing pathway alongside cysteine aminotransferase (CAT) 1. MPST acts as both a direct protein persulfidase, catalyzing protein-to-protein transpersulfidation reactions that promote cytoprotective stress responses 2, and an activatable target of ergothioneine, which enhances mitochondrial respiration and exercise performance 34. Clinically, MPST dysfunction associates with multiple pathologies. Colonic MPST deficiency exacerbates inflammatory bowel disease through AKT signaling-dependent epithelial cell apoptosis 1, while reduced MPST expression in obesity correlates with skeletal muscle dysfunction via impaired SIRT-1 persulfidation 5. MPST expression levels also serve as diagnostic and prognostic biomarkers for endometrial cancer, with associations to immune infiltration and TP53 status 6. In adipocytes, combined CBS/MPST knockdown disrupts protein persulfidation patterns and promotes inflammation 7. These findings establish MPST as a critical regulator of mitochondrial function, cellular stress adaptation, and inflammation control with therapeutic potential across metabolic, inflammatory, and neoplastic diseases.