The sodium-calcium exchanger (NCX) is an important regulator of intracellular calcium and is highly conserved across species. NCX among different species that live in diverse environments demonstrate adaptation to different conditions while maintaining a relatively high degree of identity. For further understanding of NCX temperature sensitivity, we characterized NCX gene sequences from a wide variety of genomes for analyses. However, these analyses did not lead to specific predictions of temperature sensitivity among the various homologs of NCX. By comparing NCX orthologs with different temperature dependencies yet with high genotype conservation, ten amino acids were predicted as being primarily responsible for the variation in phenotype. Mutation of these ten amino acids and activity measurement over a range of temperatures resulted in a significant change in its temperature sensitivity. Further work to elucidate the changes in NCX function at different temperatures is required to establish the specific mechanisms underlying NCX temperature dependence
