While the complete absence of PRF1 has been shown to result in prolonged engagement with the non-killed target cells yielding increased pro-inflammatory cytokines (e.g., IFN-γ) responsible for HLH, even partial disruption of perforin-mediated cytolysis by missense HLH gene mutations can delay cytolytic granule polarization yielding increased IFN-γ [29,30,31]. Here, PRF1 is linked to hemophagocytic syndrome.