KLHDC2 is a 406 amino acid protein that contains six kelch repeats. Localizing to the nucleus, KLHDC2 is widely expressed, with high levels found in muscle, heart, pancreas and liver. KLHDC2 interacts directly with CREB3, repressing CREB3-mediated transcription. Existing as two alternatively spliced isoforms, the gene encoding KLHDC2 maps to human chromosome 14, which houses over 700 genes and comprises nearly 3.5% of the human genome. Chromosome 14 encodes the presinilin 1 (PSEN1) gene, which is one of the three key genes associated with the development of Alzheimer's disease (AD). The SERPINA1 gene is also located on chromosome 14 and, when defective, leads to the genetic disorder ?-antitrypsin deficiency, which is characterized by severe lung complications and liver dysfunction.