LILRB4 as a novel immunotherapeutic target for multiple diseases.

Immune checkpoints are critical for maintaining autoimmune homeostasis and are implicated in various autoimmune diseases, with their significance increasingly recognized. Investigating the functions and mechanisms of these checkpoints is essential for the development of more effective treatments. Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4) stands out as a unique immune checkpoint, with limited expression in most normal tissues but prominent presence in various hematological and solid tumors. It is also expressed on numerous immune and stromal cells, functioning as both a "Tumor Immune Checkpoint" and a "Tumor Stromal Immune Checkpoint." Due to its distinct expression profile, LILRB4 plays a pivotal role in tumors, autoimmune diseases, allergic reactions, and the maintenance of immune homeostasis during transplantation and pregnancy. A thorough understanding of its ligands, functions, mechanisms, and ongoing therapeutic strategies targeting LILRB4 will be crucial for the development of advanced therapeutic options. This review examines LILRB4 expression and function across multiple diseases and discusses therapeutic approaches targeting LILRB4 in various contexts. Additionally, the potential of combining current drugs with LILRB4-targeted therapies is explored. Challenges in developing LILRB4-targeting drugs are also addressed, offering valuable insights for future research.