Ehlers-Danlos syndroms is a group of rare hereditary disorders involving connective tissues found in the skin, tendons, ligaments, and muscles. EDS usually results in hypermobile joints; fragile, hyperelastic skin; and easy bruising due to decreased strength and support of the vasculature. Common mutations leading to EDS phenotypes are deficiencies of lysyl-hydroxylase or pro-collagen peptidase, enzymes responsible for specific steps in collagen synthesis.

Rough endoplasmic reticulum (RER)-bound ribosomes translate pro-a collagen mRNA in the cytosol and extrude the protein into the RER. This occurs due to a distinctive N-terminal sequence that identifies the preprocollagen peptide as extracellular. After moving into the cisternae of RER, the hydrophobic signal peptide at the N-terminus is cleaved to form procollagen alpha-chains. Other posttranslational modifications include hydroxylation via lysyl hydroxylase and glycosylation of lysine residues. Within the RER, the assembly of three alpha procollagen chains begins in the C-terminus propeptide region with the formation of interchain disulfide bonds that lock the chains in place. Procollagen refers to collagen that has formed a triple helix but still contains the N-terminal and C-terminal nonhelical regions. Procollagen is exported from the cell in this form and is cleaved into collagen fibrils outside of the cell by procollagen peptidase. Lysyl oxidase then acts on neighbouring collagen fibrils to form covalent crosslinks and a mature collagen fiber.

Defective cleavage at the N-and C-termini yields the formation of more soluble collagen that does not properly crosslink with other collagen molecules. This results in the joint laxity, loose skin and easy bruisability seen in patients with EDS.