26S proteasome non-ATPase regulatory subunit 10 or gankyrin is an enzyme that in humans is encoded by the PSMD10 gene. First isolated in 1998 by Tanaka et al.; Gankyrin is an oncoprotein that is a component of the 19S regulatory cap of the proteasome. Structurally, it contains a 33-amino acid ankyrin repeat that forms a series of alpha helices. It plays a key role in regulating the cell cycle via protein-protein interactions with the cyclin-dependent kinase CDK4. It also binds closely to the E3 ubiquitin ligase MDM2, which is a regulator of the degradation of p53 and retinoblastoma protein, both transcription factors involved in tumor suppression and found mutated in many cancers. Gankyrin also has an anti-apoptotic effect and is overexpressed in certain types of tumor cells such as hepatocellular carcinoma. Function The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described. Pseudogenes have been identified on chromosomes 3 and 20. Clinical significance The proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the ubiquitin–proteasome system (UPS) and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell