How do SAP family deficiencies compromise immunity?

The signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) family of adaptors couples SLAM family receptors to activating intracellular signaling pathways that drive immune cell activation or differentiation. In the absence of SAP family adaptors, SLAM family receptors become inhibitory, possibly through coupling to the Src-homology-2-containing phosphatases. This “switch-of-function” of SLAM family receptors provides an explanation for the severe immune dysfunctions observed in humans with X-linked lymphoproliferative disease due to SAP deficiency, as well as in genetically engineered mice that lack SAP family adaptors.