Citrullination—the process of deimination of charged arginine residues to neutral citrulline residues within proteins—has been linked to numerous inflammatory and autoimmune disorders, necessitating the search for biomarker assays and potent, targeted inhibitors of this post-translational modification for therapeutic benefit. In this guide, we outline a logical screening workflow that exemplifies the use of Cayman’s assays to narrow down specific PAD4 inhibitors in the pre-clinical pursuit of effective disease treatments.