PLOD1 (procollagen-lysine,2-oxoglutarate 5-dioxygenase 1) is a lysyl hydroxylase that catalyzes hydroxylation of lysine residues in collagen alpha chains, forming hydroxylysine residues essential for collagen cross-linking stability and carbohydrate attachment 1. Beyond its classical role in collagen modification, PLOD1 exhibits unexpected glucosyltransferase activity affecting collagen fibril assembly 1. Clinically, PLOD1 is significantly upregulated across multiple cancer types including bladder cancer, hepatocellular carcinoma, thyroid carcinoma, glioma, and osteosarcoma, where elevated expression correlates with poor prognosis 23456. In the tumor microenvironment, PLOD1 expression positively correlates with immunosuppressive cell infiltration (monocytes, macrophages, tumor-associated fibroblasts) and negatively with immune-killing cells (CD8+ T cells, B cells) 2. Mechanistically, PLOD1 promotes cancer malignancy through multiple pathways: NF-κB/IL-6/STAT3-dependent metabolic reprogramming in hepatocellular carcinoma 3, Wnt/β-catenin pathway activation in thyroid carcinoma 4, HSF1 signaling in glioma 5, and β-catenin signaling in osteosarcoma 6. PLOD1 knockdown consistently reduces cancer cell proliferation, migration, and invasion across cancer types 2. In heritable vascular disease, a PLOD1 missense variant (p.Ser178Arg) segregates with familial thoracic aortic aneurysm/dissection, affecting glycosyltransferase domain folding and impairing collagen fibril girth 1.