Peptidylarginine deiminase (PAD)

Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes that catalyze the post-translational conversion (deimination/citrullination) of arginine residues into citrulline in proteins[2][5][6][7]. Humans possess five PAD isoenzymes (PAD1, PAD2, PAD3, PAD4, PAD6) with tissue- and substrate-specific roles. This modification affects protein structure, function, and protein-protein interactions. PADs are key regulators of gene expression (via direct histone modification), immune response (e.g., NETosis), and other processes such as skin barrier function and, for PAD6, female fertility. Dysregulation or overexpression of PADs, particularly PAD2 and PAD4, is implicated in numerous diseases, including autoimmune disorders (rheumatoid arthritis), cancers, and inflammatory conditions. Pharmacological inhibitors of PADs are being actively developed as therapeutic agents, particularly for autoimmune and inflammatory diseases[7][5][2]. Caveat: In therapeutics, "Peptidylarginine deiminase" without isoform specification may be ambiguous, as disease associations, tissue distribution, and druggability differ among family members[2][4][7]. For drug development and biological studies, identifying the relevant isoform (e.g., PAD4) is critical.

Other names

PADProtein-arginine deiminaseProtein arginine deiminasePADsPADI

Inhibitors covalently bind to the catalytic cysteine in the active site, blocking deimination/citrullination activity. Prevent epigenetic modification of histones, thus altering gene expression. Block NETosis by inhibiting citrullination in neutrophils.