MPC2 (mitochondrial pyruvate carrier 2) is a core component of the mitochondrial pyruvate carrier (MPC) complex, a heterodimer with MPC1 located in the inner mitochondrial membrane 1. MPC2 mediates pyruvate uptake into mitochondria, linking cytosolic glycolysis to mitochondrial oxidative metabolism and maintaining metabolic homeostasis 2. Structurally, MPC2 forms a transport channel through its interaction with MPC1's transmembrane helices, adopting alternating conformations (IMS-open, occluded, and matrix-facing states) to facilitate pyruvate translocation 1. MPC2 also functions in epigenetic-metabolic reprogramming by coupling pyruvate metabolism to ATP citrate lyase-dependent acetyl-CoA generation, which controls gene transcription and cell fate decisions in airway basal cells 3. Dysregulation of MPC2 has significant clinical implications. Reduced MPC expression correlates with cardiac metabolic remodeling in heart failure; conversely, MPC overexpression attenuates hypertrophy 4. In diabetic kidney disease, hyperglycemia-induced MPC2 acetylation impairs mitochondrial function and podocyte integrity 5. MPC2 variants show associations with schizophrenia susceptibility in Han Chinese populations 6. The complex serves as a therapeutic target, with inhibitors like UK5099 showing potential for treating diabetes, fatty liver disease, and cancers 2. Additionally, ALDH4A1 functions as an auxiliary MPC component essential for maintaining complex stability and pyruvate import 7.