KNP-I is a ubiquitously expressed mitochondrial protein that belongs to the ES1 family of proteins. It is a highly conserved protein with homologs identified in various species. This conserved nature suggests an important biological role for the KNP-I protein. The gene that encodes KNP-I (C21orf33) is located on human chromosome 21 in close proximity to a region (D21S25) associated with many genetic diseases. Down syndrome (DS), caused by an extra copy of chromosome 21, is the most common manifestation of trisomic chromosomes. It is likely that the overproduction of the C21orf33 gene product plays a role in the pathology of DS, while its chromosomal location suggests its likely involvement in D21S25 related diseases. While expressed in most tissue, highest expression of KNP-I is found in heart and muscle