Transmembrane protein (TMEM) is a type of membrane proteins, encoded by TMEM gene, also known as integral membrane protein. TMEM gene family contains various members and its encoded proteins have various functions and expressed in numerous organs. It has been proved to be widely involved in the formation of a lot of organelle membranes, enzymes, receptors and channels, mediating numerous normal physiological functions and regulating various disease processes. At present, accumulating evidences at home and abroad have shown that TMEM is involved in regulating the occurrence and development of different tumors, cardiovascular and kidney diseases. The improved understanding of molecular mechanisms of TMEM genes and proteins may provide new directions and ideas for the prevention, diagnosis and treatment of diseases. In the present review, the roles of TMEM and biological functions in various cancers, cardiovascular and kidney diseases were discussed.