Our findings are compatible with the notion that cytotoxic lymphocytes31 target neutrophils in RA by secreting perforin that creates poly-perforin pores in their plasma membrane that allow a rapid influx of calcium, which, in turn, leads to extensive intracellular citrullination by PAD4 (and perhaps PAD2). The gene discussed is PADI4; the disease is rheumatoid arthritis.