We propose the investigation of the thermodynamic and paleo-oceanographic principles of calcium (Ca) isotope fractionation (d44Ca) during biomineralization and inorganic precipitation of calcium carbonate (CaCO3). This is important because recent findings indicate that the Ca isotope system represents a new proxy for the reconstruction of past seawater temperatures and for variations of the Ca seawater concentrations throughout Earth’s history. Both aspects are crucial for paleooceanography and -climatology because they interfere with the global carbon cycle influencing the concentration of important greenhouse gases like CO2 throughout time. The concept to validate the Ca isotopes as a paleo-proxy is to test its sensitivity to temperature calibration, the preservation of primary isotope signals, the knowledge of inter-specific differences and of past initial isotope ratios. These requirements will be investigated in laboratory and culturing experiments on inorganically precipitated CaCO3 and on major groups of marine calcifying organisms previously used as proxy archives (foraminifera, bivalves, coccolithophorids). The proposed experimental cross-calibration of the Ca isotope system to temperature sensitive metal to calcium ratios (Mg/Ca, Sr/Ca, Ba/Ca, etc.) and other isotope systems (d18O, d11B, d25Mg, etc.) will be completed by field and down-core experiments offering the unique opportunity to refine their application as paleo-proxies in a multi-proxy approach.