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Ca²⁺ flux across the mitochondrial inner membrane regulates bioenergetics, cytoplasmic Ca²⁺ signals and activation of cell death pathways^,,,,,,,,,,. Mitochondrial Ca²⁺ uptake occurs at regions of close apposition with intracellular Ca²⁺ release sites^,,, driven by the inner membrane voltage generated by oxidative phosphorylation and mediated by a Ca²⁺ selective ion channel (MiCa; ref. ) called the uniporter^,, whose complete molecular identity remains unknown. Mitochondrial calcium uniporter (MCU) was recently identified as the likely ion-conducting pore^,. In addition, MICU1 was identified as a mitochondrial regulator of uniporter-mediated Ca²⁺ uptake in HeLa cells^,. Here we identified CCDC90A, hereafter referred to as MCUR1 (mitochondrial calcium uniporter regulator 1), an integral membrane protein required for MCU-dependent mitochondrial Ca²⁺ uptake. MCUR1 binds to MCU and regulates ruthenium-red …