Mitofusin-2 (Mfn2) is a highly conserved transmembrane GTPase which plays a critical role in mitochondrial fusion process. Recent data have been demonstrated that Mfn2 is involved in the regulation of several crucial cellular pathways beyond fusion, including mitochondrial metabolism, cellular signaling cascade, apoptosis and proliferation. With multiple functions and complex mechanisms, Mfn2 might play potential role in the applications in modern medicine. The structure and basic biological function of Mfn2 were summarized, furthermore, the dysfunction of Mfn2 in certain diseases and its therapeutic value were also discussed.