PPP2R2D is a regulatory subunit of protein phosphatase 2A (PP2A) that functions as a substrate-recognition component controlling multiple cellular processes. As a catalytic adapter, PPP2R2D mediates dephosphorylation of key signaling proteins across distinct physiological contexts 1. In metabolic regulation, PP2A-PPP2R2D inactivates AMP kinase by dephosphorylating Thr-172, reducing lipid catabolism; elevated PPP2R2D expression correlates with increased blood lipids in high-fat diet models 1. In immune regulation, PPP2R2D suppresses IL-2 production and constrains regulatory T cell expansion, promoting anti-tumor T cell responses in melanoma 23. Conversely, PPP2R2D promotes gastric cancer progression through mechanistic target of rapamycin (mTOR) pathway activation, with elevated expression predicting poor prognosis 4. In diabetic kidney disease, PPP2R2D dysregulation exacerbates glucose-induced inflammation via AMPK suppression, making it a therapeutic target 5. Additionally, PPP2R2D expression influences chemotherapy sensitivity in hepatocellular carcinoma, where increased levels enhance cisplatin efficacy 6. These opposing roles—tumor-suppressive in melanoma and immune contexts, tumor-promoting in gastric cancer—suggest PPP2R2D function is context-dependent and regulated by microRNAs including miR-133b and miR-5010-5p 65.