KAI1/CD82, a transmembrane protein and a member of the tetraspanin superfamily, is an evolutionally conserved molecule expressed in various tissue types. First identified to be involved in the T cell activation process, KAI1 is typically considered as a suppressor of metastasis. Most studies of KAI1 examined its function in suppressing metastasis and angiogenesis mainly in cancer cells and endothelial cells. Recently, we and others have reported that KAI1 regulates the cell cycle progression of the long-term repopulating hematopoietic stem cells (LT-HSCs) and muscle stem-progenitor cells. Thus, KAI1 has different roles in each cell and organ type.