MCU (mitochondrial calcium uniporter) is the channel-forming subunit of the mitochondrial inner membrane calcium uniporter complex, mediating calcium uptake into the mitochondrial matrix 1. MCU channel activity is regulated by calcium-sensor subunits MICU1 and MICU2/MICU3 1. Mitochondrial calcium homeostasis via MCU regulates ATP production, cytoplasmic calcium signaling, and cell death pathways 1. In cardiac tissue, MCU buffers systolic calcium rises and acts as a key regulator during acute stress, mediating rapid mitochondrial calcium loading in pacemaker cells 2. MCU upregulation through the β-adrenergic/CaMKIIδB/CREB pathway protects against stress-induced cardiac remodeling by preserving calcium homeostasis and cardiomyocyte viability 2. In skeletal muscle, MCU activity declines with aging, impairing mitochondrial respiration and contributing to sarcopenia; activating MCU with oleuropein restores mitochondrial bioenergetics and muscle performance 3. MCU regulates glucose-dependent insulin secretion in pancreatic beta-cells 1. Disease relevance includes heart failure, neurodegeneration, and Parkinson's disease, where impaired MCU function exacerbates pathology 45. Clinically, MCU dysfunction drives inflammaging in macrophages and promotes glioblastoma stem cell survival through metabolic-epigenetic axes 56.