Lymphocyte activation gene 3 (LAG-3, CD223) is an immune checkpoint control protein that negatively regulates T cells and immune responses. A CD4-like member of the Ig superfamily, LAG3 contains an extracellular IgV and three IgC domains, a transmembrane domain, and a short cytoplasmic region. LAG3 is primarily expressed by activated CD4+ T cells, CD8+ T cells, Tregs, and NK cells, where it's activated by MHC Class II molecules, its only known ligand. While it was initially shown to activate Treg cells, LAG3 can also inhibit CD8+ T cells. LAG3 is often co-expressed with PD-1 on the surface of tumor infiltrating lymphocytes, where the two proteins act independently to contribute to tumor-mediated immune suppression. Blockade of LAG3 is a promising strategy for neoplastic intervention.