In humans, the peptidyl arginine deiminases (PADIs; HGNC family link) are a family of five enzymes, PADI1-4 and PADI6. PADIs catalyze the deimination of protein L-arginine residues to L-citrulline and ammonia, generating peptidyl-citrulline on histones, fibrinogen, and other biologically relevant proteins. The human isozymes exhibit tissue-specific expression patterns [2]. Overexpression and/or increased PADI activity is observed in several diseases, including rheumatoid arthritis, Alzheimer's disease, multiple sclerosis, lupus, Parkinson's disease, and cancer [1]. Pharmacological PADI inhibition reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis [4].

* Key recommended reading is highlighted with an asterisk

* Koushik S, Joshi N, Nagaraju S, Mahmood S, Mudeenahally K, Padmavathy R, Jegatheesan SK, Mullangi R, Rajagopal S. (2017) PAD4: pathophysiology, current therapeutics and future perspective in rheumatoid arthritis. Expert Opin. Ther. Targets, 21 (4): 433-447. [PMID:28281906]

* Tu R, Grover HM, Kotra LP. (2016) Peptidyl Arginine Deiminases and Neurodegenerative Diseases. Curr. Med. Chem., 23 (2): 104-14. [PMID:26577926]

* Whiteley CG. (2014) Arginine metabolising enzymes as targets against Alzheimers' disease. Neurochem. Int., 67: 23-31. [PMID:24508404]

1. Bicker KL, Thompson PR. (2013) The protein arginine deiminases: Structure, function, inhibition, and disease. Biopolymers, 99 (2): 155-63. [PMID:23175390]

2. Jones CE, Holden S, Tenaillon L, Bhatia U, Seuwen K, Tranter P, Turner J, Kettle R, Bouhelal R, Charlton S, Nirmala NR, Jarai G, Finan P. (2003) Expression and characterization of a 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid receptor highly expressed on human eosinophils and neutrophils. Mol. Pharmacol., 63: 471-477. [PMID:12606753]

3. Kanno T, Kawada A, Yamanouchi J, Yosida-Noro C, Yoshiki A, Shiraiwa M, Kusakabe M, Manabe M, Tezuka T, Takahara H. (2000) Human peptidylarginine deiminase type III: molecular cloning and nucleotide sequence of the cDNA, properties of the recombinant enzyme, and immunohistochemical localization in human skin. J. Invest. Dermatol., 115 (5): 813-23. [PMID:11069618]

4. Moscarello MA, Lei H, Mastronardi FG, Winer S, Tsui H, Li Z, Ackerley C, Zhang L, Raijmakers R, Wood DD. (2013) Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis. Dis Model Mech, 6 (2): 467-78. [PMID:23118341]