Abstract: We described here a novel domain, CTLH, which can be found in proteins of most already-researched species currently. The domain, consisted of 58 amino acid residues, is not often-conserved in sequence (but has 5 regularly-arranged leucines that are highly conserved). However, its 3D architecture conserves greatly with a typical �U� shape (alpha helix+beta turn+alpha helix). Although the function of CTLH domain remains unknown, related studies aiming at this domain suggest it participates in the regulation of certain signaling pathways like MAPK, and is involved in some living activities of cells such as protein degradation and mitosis.