PAWR (pro-apoptotic WT1 regulator) is a tumor suppressor gene that selectively induces apoptosis in cancer cells through multiple molecular mechanisms. Primary function: PAWR promotes apoptosis by inhibiting anti-apoptotic protein BCL-2 expression and inactivating survival pathways including NF-κB and Akt signaling 12. Mechanism: PAWR functions as a transcriptional regulator that modulates WT1 activity, with chr12 studies showing its activation correlates with reduced H3K9 dimethylation and increased H3K4 dimethylation at its promoter 3. The gene activates caspase cascades and PARP cleavage, hallmarks of apoptotic cell death 2. Disease relevance: In cancer contexts, PAWR activation by small activating RNAs (saRNAs) induces growth inhibition and apoptosis in bladder and prostate cancer cells, with synergistic effects when combined with cisplatin 12. In cardiovascular disease, the circ_0068655-miR-498-PAWR axis regulates cardiomyocyte apoptosis after myocardial infarction 4. Genetic studies show PAWR polymorphisms associate with major depressive disorder susceptibility 5. Clinical significance: PAWR represents a promising therapeutic target for cancer treatment, with saRNA-mediated gene activation offering a non-vector based approach to upregulate this tumor suppressor without traditional gene therapy complications.