Homozygous genetic mutations, altering natural killer (NK) cells and CD8 T cells, in the perforin-mediated cytolytic pathway (RAB27A, PRF1, UNC13D, STX11, STXBP2, etc.)can result in the familial/primary form of HLH (pHLH), leading to unregulated immune activation, severe hyperinflammatory disease early in life, and ineffective negative feedback of the immune response [4]. This evidence concerns the gene UNC13D and hemophagocytic syndrome.