Ischemia with non-obstructive coronary artery disease (INOCA) identifies a significant proportion of patients presenting with signs and symptoms of myocardial ischemia with normal or near-normal coronary arteries at angiography. Initially believed a benign condition, it is now well-established that INOCA is associated with an increased risk for cardiovascular events. However, it is rarely correctly diagnosed. The identification of distinct signatures of circulating biomarkers and platelet alterations associated with the specific endotype of INOCA (Microvascular Angina \[MVA\]; Vasospastic Angina \[VSA\]; both MVA and VSA; and none) may help in the diagnosis of these patients as well as in the identification of specific pathophysiologic pathways and the development of future therapies. In addition, the identification of specific signatures may help in the prognostic stratification of INOCA patients, identifying those that may need more aggressive therapy and closer follow-up. Finally, the results deriving from this study may pave the way for a new pathophysiology-driven approach with cause-target therapies personalized for the specific mechanisms of INOCA. The BIOPLATINO study is the first study specifically designed to evaluate if there is a unique signature of circulating biomarkers and/or platelet function tests able to discriminate between the multiple pathogenetic mechanisms of INOCA as well as the different clinical courses. Furthermore, it may pave the way for the identification of specific pathophysiologic pathways of INOCA and the development of future therapies.