PPP2R2A encodes PP2A B55α, a regulatory subunit of protein phosphatase 2A (PP2A) that functions as a substrate-recognition component controlling critical cellular processes. Functionally, PPP2R2A plays a key role in cell cycle regulation by mediating dephosphorylation of WEE1, preventing its proteolysis and promoting G2/M checkpoint control 1. The protein also regulates chromosome 8 during mitosis 21. Clinically, PPP2R2A loss is highly prevalent in multiple cancer types. In non-small cell lung cancer (NSCLC), >40% of cases show PPP2R2A underexpression due to loss of heterozygosity 3, while 38% of high-grade serous ovarian cancers (HGSOC) exhibit deletions and downregulation 4. In breast cancer, PPP2R2A deletions were identified as putative cancer drivers 5. Mechanistically, PPP2R2A deficiency promotes cancer progression through multiple pathways: elevated PD-L1 expression via cGAS-STING activation in lung cancer 3, epithelial-mesenchymal transition (EMT) via GSK3β-β-catenin signaling 6, and enhanced replication stress sensitivity to CHK1 inhibition in ovarian cancer 7. Additionally, PPP2R2A controls immune homeostasis by regulating NAD+ biosynthesis and Th17/Treg differentiation in systemic lupus erythematosus 8. PPP2R2A deficiency also prevents PP2A-mediated dephosphorylation of oncogenic AKT1E17K, enhancing PI3K-AKT pathway signaling 9. MicroRNA-892a suppresses PPP2R2A expression to promote colorectal cancer proliferation 10.