LH3PLOD3

LH3PLOD3, also known as lysyl hydroxylase 3 (LH3), is an enzyme that plays a key role in collagen maturation and extracellular matrix integrity. It is encoded by the PLOD3 gene in humans and belongs to the lysyl hydroxylase family of enzymes involved in post-translational modification of collagen and related proteins.

LH3 is unique among its family members because it possesses both lysyl hydroxylase activity and glycosyltransferase activities. As a lysyl hydroxylase, it hydroxylates lysine residues in collagen, a modification required for proper cross-linking and stability of the collagen network. In addition, LH3 has galactosyltransferase and glucosyltransferase activities that glycosylate hydroxylysine residues, further supporting collagen maturation within the secretory pathway. These activities occur primarily in the Golgi apparatus and contribute to the structural quality of collagenous matrices.

Biochemically, LH3 is a member of the 2-oxoglutarate–dependent dioxygenase family. Its enzymatic reactions require iron (Fe2+) and ascorbate as cofactors and utilize 2-oxoglutarate to drive hydroxylation and subsequent glycosylation steps.

Genetic mutations in PLOD3 have been associated with connective tissue disorders that feature hypermobile joints, skin abnormalities, and skeletal malformations, reflecting impaired collagen modification. The clinical spectrum can resemble Ehlers-Danlos syndrome–like phenotypes, though presentations may vary.

Expression of PLOD3 is widespread, with notably high levels in fibroblasts and other tissues that produce and remodel the extracellular matrix, consistent with its essential role in collagen stability and tissue integrity.