LAT (Linker for activation of T cells, pp36) is a protein required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development. It functions in FCGR3-mediated signaling in natural killer cells and FCER1-mediated signaling in mast cells. It serves to couple activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules. Mutations in the LAT gene are believed to lead to immunodeficiency-52 (IMD52), characterized by variable autoimmune disorders with recurrent infections starting from infancy, hypogammaglobulinemia, progressive lymphopenia, and also lymphoproliferation with splenomegaly. In immunohistochemistry of normal tissue, LAT has highest membranous and cytoplasmic positivity in megakaryocytes, T-cells, NK cells, mast cells and is found in the thymus and spleen, with low levels of expression in various tissues throughout the body. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; Cell. 92 (1): 83–92, PMID: 9489702; J. Exp. Med. 213: 1185-1199, 2016. Note: Erratum: J. Exp. Med. 214: 2165 only, 2017, PMID: 27242165; J. Allergy Clin. Immun. 139: 634-642, 2017, PMID: 27522155; Online Mendelian Inheritance in Man. Johns Hopkins University, Baltimore, MD. 2018. MIM Number: 617514;