In conclusion, the clinical potential of targeting EPAC1 as a therapeutic strategy is compelling, spanning cardiovascular, metabolic, fibrotic, and oncological disorders. EPAC1 activation offers significant promise in addressing critical conditions such as heart failure, type 2 diabetes, idiopathic pulmonary fibrosis (IPF), and vascular complications through its ability to modulate intracellular calcium handling, enhance endothelial barrier function, and regulate fibroblast activity. Additionally, its role in promoting brown fat growth and beige adipogenesis introduces a compelling therapeutic avenue for combating obesity by enhancing energy expenditure and reducing metabolic complications. The elucidation of EPAC1 activation mechanisms and the partial agonist behavior of compounds like I942 provide a strong foundation for the rational design of next-generation modulators that can selectively activate EPAC1 while minimizing off-target effects. These findings not only deepen our understanding of EPAC1 dynamics but also pave the way for innovative, targeted therapies with the potential to address some of the most pressing medical challenges of our time.