Hundreds of proteins with Kelch motif have been identified in diverse organisms including viruses, plants, fungi and mammals. Although most of the Kelch proteins are not functionally characterized at present, some of the known Kelch proteins seemed to function diversely in vivo. In mammals, nearly 41 Kelch proteins have been reported and proved to mediate the protein-protein interactions, protein degradation, and gene expression and signal transmission and so on. It was proposed that the crystal structure of Kelch domain of Keap 1 could be a preferable model for researching Kelch proteins in mammals. And it was also divided these mammal Kelch proteins into three groups according to their domain organizations and paid much attention to summarize their known function in vivo.