Psmd2, encoding 26S proteasome non-ATPase regulatory subunit 2, is a key component of the ubiquitin-proteasome system. This system is crucial for regulating intracellular protein levels, and thus Psmd2 is involved in multiple cellular processes like protein homeostasis. It has been associated with pathways such as the cell cycle, antigen processing and presentation, JAK-STAT, Toll-like receptor, P53 and MAPK signaling pathways [1].

In various cancers, Psmd2 shows oncogenic properties. In bladder cancer, its overexpression promotes cancer progression and is correlated with immune infiltration, with high Psmd2 predicting unfavorable overall survival [1]. In esophageal squamous cell carcinoma, it contributes to cancer progression by repressing autophagy through activating the mTOR pathway via upregulating ASS1 [2]. In lung adenocarcinoma, upregulation of Psmd2 is linked to poor prognosis and immune infiltration, and it has a high mutation frequency [3]. In renal cell carcinoma treated with immune checkpoint and tyrosine kinase inhibitors, Psmd2 overexpression is related to resistance and decreased progression-free survival, along with changes in immune cell infiltration [4]. In nasopharyngeal carcinoma, DNAJA4 suppresses metastasis via Psmd2-mediated MYH9 degradation [5]. In breast cancer, RACK1 enhances β-catenin stability by competitively inhibiting its binding to Psmd2 [6]. In HepG2 cells, Psmd2 promotes proliferation by modulating lipid droplet metabolism [7]. In breast cancer cells, Psmd2 regulates cell proliferation and cell cycle progression by modulating p21 and p27 proteasomal degradation [8].

In conclusion, Psmd2 plays significant roles in multiple biological processes, especially in cancer-related functions. Its overexpression in various cancers promotes tumor progression, affects immune infiltration, and is associated with poor prognosis. The study of Psmd2 using in vivo models helps in understanding its role in disease development, potentially providing new therapeutic targets for cancer treatment.