PDP1 (pyruvate dehydrogenase phosphatase catalytic subunit 1) is a mitochondrial enzyme belonging to the metal-dependent PPM/PP2C phosphatase family 1. Its primary function is to dephosphorylate and reactivate the E1 component of the pyruvate dehydrogenase complex (PDC), thereby stimulating conversion of pyruvate to acetyl-CoA and promoting oxidative metabolism 2. Beyond its classical metabolic role, PDP1 exhibits unexpected functions as a scaffold protein in cancer signaling. In KRAS-mutant colorectal cancer, PDP1 enhances BRAF-MEK1 interaction to activate MAPK signaling 3. In breast cancer, PDP1 promotes progression through STAT3 pathway activation 4, while in hypoxic conditions, PDP1 supports HIF-1 transcriptional activity by maintaining acetyl-CoA levels for histone acetylation 5. Clinically, PDP1 overexpression is frequently observed in multiple malignancies including prostate cancer 6, FLT3-ITD acute myeloid leukemia 2, and breast cancer, where it correlates with poor prognosis 4. In FLT3-ITD AML, PDP1-dependent metabolic rewiring drives drug resistance to FLT3 inhibitors 2. PDP1 emerges as both a critical metabolic gatekeeper and oncogenic driver, making it a promising therapeutic target across multiple cancer types.