Lipopolysaccharide-binding protein: The missing link in sleep and inflammation

Sleep disorders represent a major global health issue, and their association with systemic low-grade inflammation has become increasingly clear. Lipopolysaccharide-binding protein (LBP), a key mediator of the immune response to gut microbiota-derived endotoxins, has emerged as a potential regulatory molecule in inflammation-related sleep disorders. Elevated LBP levels are closely linked to a variety of sleep disorders. LBP induces sleep dysregulation through multiple mechanisms, including mediating peripheral and central immune inflammation, disrupting neurotransmitter balance, and perturbing biological rhythms. Both preclinical and clinical studies have observed abnormal LBP changes in different sleep disorder models. LBP serves as a critical interface molecule connecting peripheral immune activation and central sleep regulation. Targeting the LBP signaling pathway provides a new perspective for understanding and treating immune-mediated sleep disorders, yet its translational application still faces challenges. This review systematically summarizes clinical and preclinical studies on the role of LBP in sleep, neuroimmunity, and related diseases, aiming to clarify the potential pathophysiological mechanisms of LBP in sleep disorders and explore its prospects as a therapeutic target.