LAT, also known as linker for activation of T cells, is a crucial transmembrane adapter protein. It plays a central role in T-cell antigenic signaling, acting as a key bridge between T cell-specific and general signaling pathways [2,3,4]. TCR activation is relayed via LAT, which organizes protein partners and mediates signal propagation down diverse pathways such as NFAT and AP-1 [1]. LAT is also involved in the function and differentiation of T cells, and its mutations can lead to abnormal T-cell development and function [2,5,6].

Mouse models with mutant forms of LAT have provided valuable insights. Some mutant mice showed partial or complete inhibition of T-cell development, indicating LAT's role as a positive regulator of TCR signaling [5,6]. However, LAT "knock-ins" with point mutations in the four COOH-terminal tyrosine residues developed lymphoproliferative disorders involving polyclonal T cells that produced high amounts of Th2 cytokines, revealing LAT as a negative regulator of TCR signaling and T-cell homeostasis [5,6].

In conclusion, LAT is essential for T-cell activation pathway balance and T-cell homeostasis. Mouse models, especially those with LAT mutations, have significantly contributed to understanding its role in T-cell-related immunopathologies, highlighting its importance in immunological research and potentially in developing treatments for related diseases.