Cell-cell fusion is a fascinating cellular process in the development and physiology of multicellular organisms. It is critical for fertilization, skeletal muscle development, bone remodeling, immune response, placental formation, and stem cell-mediated tissue regeneration. Failure in cell-cell fusion leads to a plethora of defects such as infertility, congenital myopathy, osteopetrosis, immune deficiency, and preterm birth. Despite the diversity of cell types that undergo fusion, all cell-cell fusion events commence from the recognition and adhesion of two fusion partners and result in the merging of their plasma membranes and the union of their cytoplasm. We are interested in uncovering the general mechanisms underlying cell-cell fusion and understanding its dysregulation in human diseases.