PDPK1 (3-phosphoinositide dependent protein kinase 1) is a serine/threonine kinase that serves as a central hub in growth signaling cascades. It phosphorylates and activates protein kinase B (AKT) at threonine 308, a critical step in the phosphoinositide 3-kinase (PI3K)/AKT pathway 1. PDPK1 regulates multiple cellular processes including glucose metabolism, cell proliferation, migration, and survival through its kinase activity and protein–protein interactions. PDPK1 is dysregulated across multiple cancer types including breast cancer, hepatocellular carcinoma, and glioblastoma. In the tumor microenvironment, PDPK1 promotes macrophage M2 polarization and glycolytic reprogramming, supporting tumor growth 23. Copper binding directly activates PDPK1 and its downstream AKT signaling, with copper transporter 1 elevated in breast cancer tissues 4. PDPK1 also facilitates immune evasion by enhancing PD-L1 expression and CD8+ T cell exhaustion 5. In coronavirus infection, PDPK1 orchestrates the switch from virophagy to mitophagy, impairing antiviral immunity 6. The small-molecule inhibitor dichloroacetate shows synergistic anti-tumor effects when combined with PI3K inhibitors such as alpelisib in breast cancer models 7. In hepatocellular carcinoma, the PDPK1 inhibitor Eliprodil combined with anti-PD-1 checkpoint blockade improved tumor control 8. These findings position PDPK1 as a therapeutic target in AKT-driven malignancies and immune-resistant tumors.