Calmyrin is identified as a calcium-binding protein with a molecular weight of ~22kD. Calmyrin displays various properties, including myristoylation, membrane-association, and colocalization with presenilin-2 (PS-2). Functionally, like presenilin, calmyrin causes cell death when overexpressed in HeLa cells. Interestingly, calmyrin coexpresses with PS-2, and induces additive effects in apoptosis. These results indicate diverse roles of calmyrin in cell signaling, cell death and Alzheimer disease through the modulation of presenilin function.