Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor primarily expressed on natural killer (NK) cells and antigen-experienced T cells, including CD8+ T cells, CD4+ T cells, and regulatory T cells (Tregs). It functions as a type II transmembrane glycoprotein with an extracellular C-type lectin domain and an intracellular immunoreceptor tyrosine-based inhibitory motif (ITIM). KLRG1 binds to cadherins (such as E-cadherin, N-cadherin, and R-cadherin) on antigen-presenting cells (APCs) or tumor cells, inhibiting immune cell activation, proliferation, and cytotoxicity through the PI3K/AKT and AMPK pathways. In disease contexts, KLRG1 is implicated in various immune responses. In autoimmune diseases like primary biliary cholangitis and systemic lupus erythematosus, its expression correlates with disease severity. In cancer, KLRG1+ T cells are associated with immune evasion, and high KLRG1 expression in tumors is linked to poor prognosis. KLRG1 is also involved in viral infections, where it can inhibit T cell function and promote immune exhaustion. Ongoing research explores KLRG1 as a potential therapeutic target for modulating immune responses in cancer and autoimmune diseases.