Citrullination under physiological and pathological conditions

Citrullination, one of the enzymatic posttranslational modifications has become a hot topic of recent research as it is involved in various physiological and pathological processes. Antibodies against citrullinated proteins called anti-citrullinated protein antibodies, are the hallmark (diagnostic and prognostic factors) of rheumatoid arthritis, and are specific for the disease. Citrullination has an important role in the normal function of the immune system, skin keratinization, the insulation of neurons and the plasticity of the central nervous system including its essential role in gene regulation. Abnormal citrullination has been proposed to play a role in multiple sclerosis and Alzheimer's disease, and recent research has drawn attention to its implication in tumorigenesis. Still, it is unclear whether citrullination is the cause or the consequence of these pathological alterations. Here, we discuss crucial aspects of citrullination during both physiological and pathological conditions.