▪ Abstract Intein is the protein equivalent of intron and has been discovered in increasing numbers of organisms and host proteins. A self-splicing intein catalyzes its own removal from the host protein through a posttranslational process of protein splicing. A mobile intein displays a site-specific endonuclease activity that confers genetic mobility to the intein through intein homing. Recent findings of intein structure and the mechanism of protein splicing illuminated how inteins work and yielded clues regarding intein's origin, spread, and evolution. Inteins can evolve into new structures and new functions, such as split inteins that do trans-splicing. The structural basis of intein function needs to be identified for a full understanding of the origin and evolution of this marvelous genetic element.