KLRG1 is an immune checkpoint receptor expressed in NK and T-cell subsets, playing a key role in regulating immune cell activation and proliferation. It has emerged as a significant biomarker and therapeutic target in various diseases, including autoimmune disorders, infectious diseases, and cancers. KLRG1 inhibits immune cell function by interacting with its ligand, cadherin, and modulates signaling pathways such as PI3K/AKT and AMPK. Inhibiting KLRG1 has shown promise in enhancing immune responses and improving vaccine efficacy in preclinical models. However, KLRG1 inhibitors are not yet approved for human use, and further research is needed to fully understand its role in different diseases. KLRG1 expression varies among immune cell types and disease states, suggesting diverse regulatory mechanisms. In autoimmune diseases, increased KLRG1 expression is associated with disease severity, while in infections and cancers, it may contribute to immune evasion. KLRG1 is also involved in tumor progression and immune suppression, making it a potential therapeutic target. Recent studies highlight its potential in immunotherapy, particularly in combination with other checkpoint inhibitors. Despite these findings, more research is needed to clarify the clinical significance of KLRG1 as a biomarker and therapeutic target. Current efforts focus on developing KLRG1-targeted therapies, with some clinical trials underway for autoimmune diseases and cancers. The role of KLRG1 in immune regulation and disease progression remains an active area of research.KLRG1 is an immune checkpoint receptor expressed in NK and T-cell subsets, playing a key role in regulating immune cell activation and proliferation. It has emerged as a significant biomarker and therapeutic target in various diseases, including autoimmune disorders, infectious diseases, and cancers. KLRG1 inhibits immune cell function by interacting with its ligand, cadherin, and modulates signaling pathways such as PI3K/AKT and AMPK. Inhibiting KLRG1 has shown promise in enhancing immune responses and improving vaccine efficacy in preclinical models. However, KLRG1 inhibitors are not yet approved for human use, and further research is needed to fully understand its role in different diseases. KLRG1 expression varies among immune cell types and disease states, suggesting diverse regulatory mechanisms. In autoimmune diseases, increased KLRG1 expression is associated with disease severity, while in infections and cancers, it may contribute to immune evasion. KLRG1 is also involved in tumor progression and immune suppression, making it a potential therapeutic target. Recent studies highlight its potential in immunotherapy, particularly in combination with other checkpoint inhibitors. Despite these findings, more research is needed to clarify the clinical significance of KLRG1 as a biomarker and therapeutic target. Current efforts focus on developing KLRG1-targeted therapies, with some clinical trials underway for autoimmune diseases and cancers. The role of KLRG1 in immune regulation and disease progression remains an active area of research.