Calcium mediates numerous functions in the human body. The two main organelles that regulate cellular calcium ion concentration are the mitochondria and endoplasmic reticulum (ER). Mitochondria take up calcium from the cytosol and regulate calcium-mediated cell signaling pathways. Calcium is involved in two primary mitochondrial functions: apoptosis and cellular respiration. The mitochondrial calcium uniporter (MCU) is the ion channel in the mitochondria for calcium uptake and regulation. After decades of research, the biological characteristics and functions of MCU’s have only recently been elucidated. This review focused on the fundamental role of MCU’s in calcium uptake and its biochemical properties based on its protein structure and aims at helping researchers learn more about how MCU regulates a Ca²⁺ uptake.