In eukaryotic cells, selective breakdown of cellular proteins is ensured by their ubiquitination and subsequent degradation by the 26S Proteasome. The 26S Proteasome is a protease complex that selectively breaks down proteins that have been modified by polyubiquitin chains. It is made up of two multisubunit complexes: the 20S Proteasome chamber, which serves as the proteolytic core of the complex and two 19S regulatory particles which recognize and unfold ubiquitinated proteins. PSMD3 (proteasome (prosome, macropain) 26S subunit, non-ATPase, 3), also known as S3, P58 or RPN3, is a 534 amino acid regulatory component of the 26S Proteasome that consists of one PCI domain. PSMD3 is encoded by a gene located on human chromosome 17, which comprises over 2.5% of the human genome and encodes over 1,200 genes.