HLH-related primary immunodeficiency syndromes are associated with mutations in genes involved in the cytotoxic pathway, including LYST (encoding for Lyst, involved in Chédiak-Higashi syndrome), RAB27A (Rab27a, Griscelli syndrome 2), AP3B1 (AP3, Hermansky-Pudlak syndrome type 2), SH2D1A (SAP, X-linked lymphoproliferative syndrome (XLP)-1), and BIRC4 (XIAP, XLP-2). This evidence concerns the gene SH2D1A and X-linked lymphoproliferative disease.