PDP2 is a mitochondrial metal-dependent Ser/Thr protein phosphatase belonging to the PPM family 1 that catalyzes dephosphorylation and reactivation of pyruvate dehydrogenase (PDH), thereby promoting the conversion of pyruvate to acetyl-CoA and facilitating oxidative phosphorylation 2. As a member of the 20 mammalian PPM phosphatases, PDP2 contains conserved catalytic domains binding manganese/magnesium ions and functions as a single subunit enzyme involved in cellular metabolism 1. PDP2 plays a crucial regulatory role in T cell metabolism and Th17 differentiation by controlling the PDH bifurcation point between glycolysis and oxidative metabolism 2. The transcription factor ICER/CREM directly suppresses PDP2 expression in Th17 cells; forced PDP2 expression reduces Th17 differentiation and experimental autoimmune encephalomyelitis, while PDP2 suppression enhances Th17 responses 2. PDP2 expression is decreased in memory Th17 cells from systemic lupus erythematosus patients 2. Beyond T cell metabolism, PDP2 regulates glucose metabolism in multiple cell types. In breast cancer, PDP2 dephosphorylates ACSL4 to inhibit ferroptosis 3. PDP2 expression is controlled by the RNA-binding protein AUF1, which promotes decay of PDP2 mRNA during cellular senescence 4. Additionally, PDP2 modulates glycolytic metabolism in neuroblastoma and is associated with Parkinson's disease progression 5, 6.