Citrullination: a posttranslational modification in health and disease.

Posttranslational modifications are chemical changes to proteins that take place after synthesis. One such modification, peptidylarginine to peptidylcitrulline conversion, catalysed by peptidylarginine deiminases, has recently received significant interest in biomedicine. Introduction of citrulline dramatically changes the structure and function of proteins. It has been implicated in several physiological and pathological processes. Physiological processes include epithelial terminal differentiation, gene expression regulation, and apoptosis. Rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease are examples of human diseases where protein citrullination involvement has been demonstrated. In this review, we discuss our current understanding on the importance of protein deimination in these processes. We describe the enzymes catalyzing the reaction, as well as their known protein substrates. We review the citrullinated peptide epitopes that are proposed as disease markers, specifically recognized in certain human autoimmune disorders. The potential autopathogenic role of citrullinated epitopes is also discussed.