A-kinase anchoring proteins (AKAPs) play crucial roles in regulating compartmentalized multi-protein signaling networks related to PKA-mediated phosphorylation. The mitochondrial AKAP - AKAP1 proteins are enriched in heart and play cardiac protective roles. This review aims to thoroughly summarize AKAP1 variants from their sequence features to the structure-function relationships between AKAP1 and its binding partners, as well as the molecular mechanisms of AKAP1 in cardiac hypertrophy, hypoxia-induced myocardial infarction and endothelial cells dysfunction, suggesting AKAP1 as a candidate for cardiovascular therapy.