Background:The role of calcium-regulated kinases in lineage specific cardiac progenitor cells (CPCs) is unknown. Results: Nuclear calcium/calmodulin-dependent kinase II ␦B isoform (CaMKII␦B) is up-regulated during cardiac progenitor commitment, which facilitates survival and differentiation of CPCs. Conclusion: Augmentation of CaMKII␦B in CPCs enhances differentiation into the cardiomyogenic lineages. Significance: The ability of CaMKII␦B to enhance cardiomyogenesis maybe relevant for regenerative-based therapies.