APPL1 is a connexin that directly connects with adiponectin receptor, containing three main functional domains, i.e. phosphotyrosine binding domain (PTB) close to carboxyl terminus, Bin1/amphiphysin/rvs167 (BAR) close to amino terminus, and pleckstrin homology domain (PH) between PTB and BAR. APPL1 expresses in different tissues and organs, regulating insulin-signaling pathway and adiponectin-signaling pathway. APPL1 plays critical roles in processes such as cell apoptosis, cell survival, and chromatin remodeling by directly interacting with membrane receptors and signaling proteins, as well as fighting against myocardial apoptosis, atrial hypertrophy and fibrosis, and heart failure via relevant pathways. APPL1 can protect vessels through involving in regulating the production of endothelial cell NO and coordinating the balance between NO and vasoconstrictor effectors. APPL1 signal transduction pathway also plays an important role in mediation of the heart metabolism via adiponectin.