Protein Arginine Deiminases (PADs) are guanidino-modifying enzymes belonging to the amidinotransferase superfamily and are designated PAD1-4 and PAD6. PAD enzymes catalyze the conversion of specific arginine residues to citrulline in a calcium-dependent manner. All enzymes are cytosolic except for PAD4 which is localized in the nucleus. PAD2 is the most widely expressed member and also the most conserved across mammalian species, implying it is the ancestral homologue of the PADs. Overexpression of PAD2 results in myelin loss in a transgenic model, potentially linking PAD2 activity to multiple sclerosis. It has also been shown to modify vimentin and β/γ-actin, potentially aggravating the autoantigen response in rheumatoid arthritis. PAD2 may also play a role in transcriptional regulation, as it has been shown capable of citrullinating histones, particularly H3 during mammalian reproductive cycles, when it is transcriptionally activated in the nucleus.