PLOD2 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 2) is a key collagen-modifying enzyme that catalyzes hydroxylation of lysine residues in collagen molecules at -Xaa-Lys-Gly- sequences. These hydroxylysine residues serve as critical attachment sites for carbohydrate units and are essential for stabilizing intermolecular collagen cross-links 1. PLOD2 functions in the endoplasmic reticulum and Golgi apparatus during collagen biosynthesis and post-translational modification of type I collagen 2. The enzyme's expression is tightly regulated by hypoxia through HIF-1α signaling 34. Under hypoxic conditions, PLOD2 translation is enhanced via RBM4 and eIF4E2-dependent mechanisms, enabling ECM remodeling critical for cancer cell migration and invasion 4. Clinically, PLOD2 dysregulation is associated with multiple pathologies. Mutations in PLOD2 cause Bruck syndrome 2, a rare autosomal recessive disorder characterized by bone fragility and joint contractures due to impaired type I collagen biosynthesis 2. Additionally, PLOD2 is frequently overexpressed in various cancers, where it promotes collagen stabilization and metastatic progression, correlating with poor prognosis 135. PLOD2 inhibition shows promise as an anti-metastatic therapeutic strategy.