The function of LAG3 (lymphocyte activating 3, ENSG00000089692) is as follows. [Lymphocyte activation gene 3 protein]: Inhibitory receptor on antigen activated T-cells (PubMed:20421648, PubMed:35761082, PubMed:7805750, PubMed:8647185). Delivers inhibitory signals upon binding to ligands, such as MHC class II, its main ligand present at the surface of antigen-presenting cells (APCs), and FGL1, which is secreted by hepatocytes and certain types of tumor cells (PubMed:30580966, PubMed:32920841, PubMed:35761082, PubMed:39671469, PubMed:7589152, PubMed:8647185, PubMed:9159144). Ligand-binding initiates a signaling that inhibits the T-cell receptor (TCR) in the immunological synapse, preventing T-cell activation (PubMed:40101708). Mechanistically, ligand-binding promotes (1) ubiquitination of the KIEELE motif, unleashing the RRFSALE motif from the membrane and (2) leading to the formation of condensates with the TCR component CD3E, thereby disrupting the association between CD3E and LCK and preventing TCR activation (PubMed:40101708, PubMed:40592325). May inhibit antigen- specific T-cell activation in synergy with PDCD1/PD-1 (By similarity). Negatively regulates the proliferation, activation, effector function and homeostasis of both CD8(+) and CD4(+) T-cells (PubMed:20421648, PubMed:7805750, PubMed:8647185). Also mediates immune tolerance: constitutively expressed on a subset of regulatory T-cells (Tregs) and contributes to their suppressive function (By similarity). Also acts as a negative regulator of plasmacytoid dendritic cell (pDCs) activation (By similarity). {ECO:0000250|UniProtKB:Q61790, ECO:0000269|PubMed:20421648, ECO:0000269|PubMed:30580966, ECO:0000269|PubMed:32920841, ECO:0000269|PubMed:35761082, ECO:0000269|PubMed:39671469, ECO:0000269|PubMed:40101708, ECO:0000269|PubMed:40592325, ECO:0000269|PubMed:7589152, ECO:0000269|PubMed:7805750, ECO:0000269|PubMed:8647185, ECO:0000269|PubMed:9159144}. The LAG3-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:35981087, PubMed:40101708). The blockage of the LAG3- and PDCD1-mediated pathways results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (PubMed:35981087, PubMed:40101708). . [Secreted lymphocyte activation gene 3 protein]: May function as a ligand for MHC class II (MHC-II) on antigen-presenting cells (APC), promoting APC activation/maturation and driving Th1 immune response. .