PPP2R3A (protein phosphatase 2 regulatory subunit B''alpha) is a regulatory component of protein phosphatase 2A (PP2A) that modulates substrate selectivity, catalytic activity, and subcellular localization of the catalytic enzyme. It functions as a negative regulator of cell growth and division 1. Mechanistically, PPP2R3A regulates multiple cellular processes through distinct pathways. In hepatocellular carcinoma, PPP2R3A promotes glycolysis by regulating hexokinase 1 (HK1), with PPP2R3A overexpression increasing HK1 expression, glucose uptake, and lactate production 2. In cardiac myocytes, PPP2R3A silencing inhibits cell proliferation, arrests the cell cycle in S phase, and promotes apoptosis, with interaction partners including COL1A2, GIPC1, and BCL6 3. In endothelial cells, PPP2R3A downregulation increases blood-brain barrier permeability through the NOVA2/PART1/PPP2R3A/p-NFκB-p65 pathway during amyloid-β stimulation 4. Clinical relevance emerges across multiple diseases. PPP2R3A expression is elevated in hepatocellular carcinoma tissues, where knockdown suppresses proliferation, migration, invasion, and xenograft tumor growth 5. In celiac disease, PPP2R3A is constitutively downregulated in intestinal epithelium, suggesting genetic involvement in disease pathogenesis 1. Promoter hypermethylation of PPP2R3A occurs in over 60% of colon cancer cases, correlating with tumor suppressor function 6. Genome-wide association studies identify PPP2R3A as a shared genetic risk factor for kidney diseases and sepsis, suggesting pleiotropic effects 7. PPP2R3A is also proposed as a druggable target for coronary artery disease 8.