PLOD3 encodes a multifunctional enzyme essential for collagen post-translational modifications and extracellular matrix integrity. The enzyme catalyzes hydroxylation of lysine residues in procollagen to form hydroxylysine, followed by glycosylation reactions that add galactose and glucose moieties to create glucosylgalactosyl-hydroxylysine residues 1. These modifications are crucial for proper collagen biosynthesis, basement membrane formation, and type IV collagen secretion. PLOD3 expression occurs in developing tissues including cochlea, eyes, skin, heart, and cartilage, reflecting its broad physiological importance 2. Pathogenic variants cause BCARD syndrome, a connective tissue disorder characterized by ocular abnormalities with retinal detachment risk, sensorineural hearing loss, skeletal deformities, vascular complications, and developmental features resembling Stickler syndrome with variable Ehlers-Danlos and epidermolysis bullosa features 2. Beyond Mendelian disease, PLOD3 overexpression promotes cancer progression in colorectal cancer and glioblastoma through mechanisms involving epithelial-mesenchymal transition, autophagy regulation, and immune microenvironment modulation 345. The protein's role in extracellular matrix remodeling and its association with both rare genetic disorders and common cancers highlight its clinical significance as both a diagnostic biomarker and potential therapeutic target.