PRODH (proline dehydrogenase 1) is a mitochondrial FAD-dependent enzyme that catalyzes the initial step of proline catabolism, converting proline to delta-1-pyrroline-5-carboxylate [UniProt]. The enzyme localizes to the mitochondrial inner membrane and functions as an oxidoreductase, playing a critical role in limiting mitochondrial oxidative phosphorylation and reactive oxygen species (ROS) production 1. PRODH is dramatically upregulated in naive human embryonic stem cells, where it safeguards pluripotency by preventing excessive ROS-induced autophagy, DNA damage, and apoptosis 1. In cancer biology, PRODH expression is elevated in metastases compared to primary tumors, and proline catabolism via PRODH supports metastasis formation; inhibiting PRODH impairs lung metastasis development in mouse models 2. PRODH also participates in maintaining mitochondrial redox homeostasis by restraining polyamine-driven proline catabolism 3. Clinically, PRODH mutations cause hyperprolinemia type 1 [NCBI]. Regarding neuropsychiatric disease, PRODH polymorphisms, particularly rs372055, show association with schizophrenia risk in Asian populations 4, though evidence for loss-of-function variants conferring schizophrenia susceptibility remains controversial 5. PRODH is identified as a potential biomarker in glutamine metabolism networks associated with diabetic foot ulcer complications 6.