Psme1, encoding proteasome activator subunit PA28α, is a key regulator of the proteasome, which plays a central role in proteostasis. The PA28α/β complex (PSME1/PSME2) impacts proteasomal degradation, and thus is involved in various biological pathways, influencing processes like cell differentiation, development, and immune response [1,3,4,5]. Genetic models, such as KO/CKO mouse models, can be valuable in further elucidating its functions.

In osteoporosis, protein levels of PSME1/2 increase, mainly accumulating in osteoblasts and osteoclasts. Treatment with PSME1/2 recombinant protein inhibits osteogenesis and promotes osteoclast formation in vitro, as it inhibits β -catenin protein expression, limiting Wnt/β -catenin signaling. Carfilzomib, a proteasome inhibitor, targets PSME1/2, increasing β -catenin protein levels, activating Wnt/β -catenin signaling, and promoting osteogenesis while inhibiting osteoclastic differentiation in vivo [1]. In HBV infection, PSME1 expression is up-regulated. PSME1 interacts with HBV core protein (HBc), inhibiting its degradation by the 26S proteasome, thus promoting HBV replication. PSME1 silencing inhibits HBV transcription in the HBV infection system [2].

In summary, Psme1 is crucial in regulating proteasomal function, influencing processes like bone metabolism and viral replication. Research using KO/CKO mouse models could potentially provide more insights into its role in osteoporosis and HBV-related diseases, offering new therapeutic strategies for these conditions.