The 26S proteasome is a highly abundant ~2 MDa complex that serves as the proteolytic arm of the ubiquitin-proteasome system. It consists largely of two sub-complexes, the 19S regulatory particle (RP) and the 20S catalytic core particle (CP), and in many cases two RPs cap either end of a CP. The CP is made of two stacked beta-rings that contain the catalytic sites, each of which is made of seven subunits (b1-7), flanked on either side by two alpha-rings, which are also made of seven subunits each (a1-7). Thus, the structure of the 20S CP is a1-7b1-7b1-7a1-7. The RP includes a base and a lid. The base, in part, is composed of a hexametric ring of ATPases that function to unfold the substrate and open the gate of the interlacing N-terminal segments of thee alpha-subunits, thus allowing entry of the unfolded substrate into the catalytic chamber. The lid is predominantly involved in specific recognition of the ubiquitin signal (1). In addition to the 19S cap, other proteins and complexes, such as proteasome activator 28 (PA28/11S), bind to the end of the 20S cylinder and activate it by facilitating opening of the gate. Furthermore, proteasome-associated DUBs and E3s can remodel substrate-anchored polyubiquitin chains, which may modulate their susceptibility to degradation (2). PSMA3 (HC8/a7) is an alpha subunit of the 20S proteasome. PSMA3 lacks any known proteolytic activity but may have an important role in the intiation of ring formation and 20S proteasome assembly (3). Research studies have demonstrated that PSMA3 serves as a receptor within the proteasome, recruiting substrates that are destined for degradation in a ubiquitination-independent manner (4,5).