L3HYPDH (trans-L-3-hydroxyproline dehydratase) is a hydro-lyase enzyme that catalyzes the dehydration of trans-3-hydroxy-L-proline to Δ(1)-pyrroline-2-carboxylate, functioning as the first characterized human enzyme acting on this substrate 1. The enzyme likely degrades dietary trans-3-hydroxy-L-proline and metabolites from collagen-IV degradation 1. Beyond its canonical metabolic role, L3HYPDH functions as an interferon-stimulated gene (ISG) that inhibits enterovirus 71 (EV71) replication by specifically suppressing EV71 internal ribosome entry site (IRES)-mediated protein translation, with amino acids 61-120 and 295-354 being critical for antiviral activity 2. Emerging evidence indicates L3HYPDH has broader disease relevance: genetic variants (rs76119478) associated with L3HYPDH mRNA expression correlate with working memory performance through effects on left cuneus volume 3, and L3HYPDH has been identified as a potential novel schizophrenia risk gene in immune cell transcriptome-wide association studies 4. Additionally, L3HYPDH appears as a significant autoantibody biomarker in acromegaly patients 5. These findings suggest L3HYPDH functions both in amino acid metabolism and innate immunity, with potential implications for neuropsychiatric and endocrine disorders.