Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2)

Procollagen-lysine,2-oxoglutarate 5-dioxygenase 2 (PLOD2) is a membrane-bound homodimeric enzyme of the 2-oxoglutarate-dependent dioxygenase superfamily, primarily localized in the rough endoplasmic reticulum. PLOD2 catalyzes the hydroxylation of lysine residues within the telopeptide regions of collagen, a process essential for generating hydroxylysine residues that serve as sites of carbohydrate attachment and stable pyridinoline cross-links. This enzymatic modification is crucial for proper collagen fibril formation, extracellular matrix stability, and tissue integrity. Mutations in PLOD2 cause Bruck syndrome and are implicated in other connective tissue disorders such as osteogenesis imperfecta and Ehlers-Danlos syndrome type VIB. PLOD2 is strongly upregulated in various cancers where it promotes increased collagen cross-linking, matrix stiffening, and tumor cell invasion and metastasis, as well as in fibrotic diseases. It is also regulated by hypoxia, TGF-β, HIF-1α, and other transcriptional and epigenetic factors. As a result, PLOD2 is recognized as a therapeutic target for both fibrotic and metastatic diseases, and pharmacological inhibition of PLOD2 is being explored for clinical benefit in these contexts.

Other names

Lysyl hydroxylase 2LH2Telopeptidyl lysyl hydroxylaseTelopeptide lysyl hydroxylaseProcollagen lysyl hydroxylase 2Lysyl hydroxlase 2TLHBRKS2

Minoxidil inhibits PLOD2 expression, reduces collagen cross-linking, suppresses downstream signaling pathways such as AKT/mTOR, and decreases metastatic potential in cancer models. (Experimental PLOD2 inhibitors under investigation aim to block its enzymatic activity to reduce collagen cross-link formation and matrix stiffening)