SH2D1A and X-linked lymphoproliferative disease: Through its direct association with the CD3ζ chain, SAP was found to play a central role in T cell activation.292 Indeed, mutations or deletions of the SH2D1A gene encoding SAP resulted in X-linked lymphoproliferative syndrome-1 (XLP1), which is characterized by immunodeficiency due to a specific defect in T cells (apoptosis resistance and impaired interaction with B cell), reduced cytotoxicity of natural killer cells, a decrease in B cell functions, and defective NKT cell development.293,294