NEDL2 is a 1,572 amino acid cytoplasmic protein that is involved in protein modification and ubiquitination and exists as two alternatively spliced isoforms. NEDL2 acts as an E3 ubiquitin-protein ligase that enhances p73 transcription activation, ubiquitination and stabilization, and is highly expressed in adult heart, lung and brain. Containing one C2 domain, two WW domains and a single HECT (E6AP-type E3 ubiquitin-protein ligase) domain, NEDL2 is encoded by a gene that maps to human chromosome 2, which consists of 237 million bases, encodes over 1,400 genes and makes up approximately 8% of the human genome. A number of genetic diseases are linked to genes on chromosome 2 including Harlequin icthyosis, sitosterolemia and Alstr鰉 syndrome.