The KRAB domain had initially been identified in 1988 as a periodic array of leucine residues separated by six amino acids 5’ to the zinc finger region of KOX1/ZNF10 coined heptad repeat of leucines (also known as a  leucine zipper). Later, this domain was named in association with the C2H2-Zinc finger proteins Krüppel associated box (KRAB). The KRAB domain is confined to genomes from tetrapod organisms. The KRAB containing C2H2-ZNF genes constitute the largest sub-family of zinc finger genes. More than half of the C2H2-ZNF genes are associated with a KRAB domain in the human genome. They are more prone to clustering and are found in large clusters on the human genome.
The KRAB domain presents one of the strongest repressors in the human genome. Once the KRAB domain was fused to the tetracycline repressor (TetR), the TetR-KRAB fusion proteins were the first engineered drug-inducible repressor that worked in mammalian cells. Two distinct types of KRAB A domains can be structurally and functionally distinguished. Ancestral KRAB A domains present in human PDRM9 proteins are even evolutionary conserved in mussel genomes. Modern KRAB A domain sequences are found in coelacanth latimeria chalumnae and in Lungfish genomes.