Leukocyte immunoglobulin (Ig)-like receptor B4 (LILRB4) is a member of leukocyte Ig-like receptors (LILRs), which associate with membrane adaptors to signal through multiple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Under physiological conditions, LILRB4 plays a very important role in the function of the immune system through its expression on various immune cells, such as T cells and plasma cells. Under pathological conditions, LILRB4 affects the processes of various diseases, such as the transformation and infiltration of tumors and leukemias, through various signaling pathways. Differential expression of LILRB4 is present in a variety of immune system diseases, such as Kawasaki disease, systemic lupus erythematosus (SLE), and sepsis. Recent studies have shown that LILRB4 also plays a role in mental illness. The important role of LILRB4 in the immune system and its differential expression in a variety of diseases make LILRB4 a potential prophylactic and therapeutic target for a variety of diseases.