PRODH2 (proline dehydrogenase 2) is a mitochondrial oxidoreductase that catalyzes the dehydrogenation of trans-4-L-hydroxyproline to delta-1-pyrroline-3-hydroxy-5-carboxylate using ubiquinone-10 as the terminal electron acceptor 1. The enzyme preferentially metabolizes hydroxyproline (Hyp), a product of collagen degradation, over proline 1. PRODH2 has emerged as a critical metabolic regulator with immunological relevance. Overexpression of PRODH2 in CAR-T cells enhances their anti-tumor efficacy by reshaping metabolic and immune functions 23. In the bone microenvironment, PRODH2-mediated Hyp metabolism generates acetyl-CoA, which promotes osteoclast differentiation and breast cancer bone metastasis through activation of ferroptosis-suppressing and pro-inflammatory pathways 4. Clinically, biallelic PRODH2 mutations cause autosomal-recessive hydroxyprolinemia, an asymptomatic condition with estimated prevalence of 1 in 47,300 newborns 5. PRODH2 also represents a therapeutic target for primary hyperoxaluria, as hydroxyproline catabolism contributes significantly to glyoxylate and oxalate burden 1. Evidence suggests PRODH2 involvement in schizophrenia pathophysiology 6, and its expression is modulated by epigenetic mechanisms relevant to necrotizing enterocolitis 7.