Abstract: Mitochondria are highly dynamic organelles with constant fusion and fission. Mitofusin-2( Mfn2) is widely distributed on the outer membrane of mitochondria and mitochondria-associated endoplasmic reticulum membrane( MAM) with multiple functions to sustain normal cell function. In addition to promoting mitochondrial fusion,Mfn2 also participates in injured mitochondria mitophagy,tethers endoplasmic reticulum( ER) to mitochondria,sustains ER structure and functions and plays critical roles in several cell death pathways( including apoptosis and necrotic cell death) by mediating mitochondrial outer membrane permeabilization and facilitating opening of the mitochondrial permeability pore( m PTP)during death. Moreover,Mfn2 gene regulates vascular smooth muscle cell( VSMC) proliferation via Ras-Raf-ERK / MAPK and Ras-PI3K-Akt pathways. Mfn2 is associated with cardiac diseases including hypertension,pulmonary artery hypertension,atherosclerosis,dilated cardiomyopathy,acute ischemic reperfusion injury,cardiac hypertrophy,heart failure and major metabolic disturbance such as diabetes and obesity. Exploration of the relationships between Mfn2 and cardiac diseases may provide therapeutic potentials for cardiac diseases.