Calcium ions, Ca2+, serve as important signaling molecules specific for the eukaryotic cell for multiple purposes including propagating signal transduction pathways and initiating muscle contractions. In the presence of Ca2+, the family of membrane binding proteins called annexins have an enhanced ability to bind to negatively charged phospholipids within the cellular membrane. A member of the annexin family, annexin A2, is suggested to play a role in muscle repair by interacting with the protein dysferlin which is associated with diseases called dysferlinopathies. Dysferlinopathy is a type of muscular dystrophy in which the muscle is weakened or atrophied due to a reduction or absence of dysferlin. In order to better understand the role of annexin A2 in membrane repair, it is necessary to examine the binding properties of this protein in response to the initiating trigger for membrane repair, the influx of calcium ion. Therefore, the interaction between annexin A2 and Ca2+ was investigated. Isothermal titration calorimetry (ITC) and Differential Scanning Calorimetry (DSC) were used to identify the number of Ca2+ molecules that annexin A2 binds, the sensitivity of annexin A2 to calcium (its affinity) and the thermodynamic mechanism by which this protein senses and responds to calcium ion (enthalpy). Describing details of calcium ion binding by annexin A2 will lead to a better understanding of muscle membrane repair mechanism which can be applied to diseases such as muscular dystrophy. As in this disease, the damage is due to an influx of too much calcium ion, essentially poisoning the cell in a way that is not understood.