PSMD12 is a non-ATPase subunit of the 26S proteasome complex essential for ATP-dependent degradation of ubiquitinated proteins and maintenance of protein homeostasis. Beyond its canonical proteasomal role, PSMD12 functions as a regulatory hub in multiple disease contexts. In viral pathology, PSMD12 acts as a positive host factor for influenza A virus replication by mediating K63-linked ubiquitination of the viral M1 protein at K102, promoting virus-like particle assembly and budding 1. This interaction represents a novel antiviral drug target. PSMD12 dysregulation is implicated in multiple malignancies. In pancreatic cancer, PSMD12 overexpression promotes tumor growth by interacting with CDKN3 and reducing its ubiquitination, stabilizing this cyclin-dependent kinase inhibitor 2. Similarly, in hepatocellular carcinoma and lung adenocarcinoma, PSMD12 promotes progression by stabilizing CDK1, accelerating G2/M cell cycle transition 3, 4. In non-small cell lung cancer, PSMD12 activates the Nrf2/TrxR1 antioxidant pathway to enhance malignant phenotypes 5. PSMD12 overexpression also disrupts blood-brain barrier integrity in lung adenocarcinoma, facilitating brain metastasis 6. Germline PSMD12 variants cause Stankiewicz-Isidor syndrome, a developmental disorder with potential growth abnormalities 7. Additionally, de novo PSMD12 variants have been associated with syndromic craniosynostosis, implicating PSMD12 in chr17-regulated developmental processes 8.