To investigate how PR3 interacts with the ANCAs during inflammation and whether these interactions can be intervened by therapeutics, we developed a human PR3 mutant (iPR3-Val103) with a Val103—the major polymorphic variant at the Val/Ile polymorphic site of wild-type human PR3 [Val/Ile in GPA patients: 64.7/35.3 (6)]—and a Ser195Ala mutation that alters the charge relay network of Asp102, His57, and Ser195 and thereby disables catalytic functioning in PR3 (7–10). The gene discussed is PRTN3; the disease is granulomatosis with polyangiitis.