Lipopolysaccharide-responsive and beige-like anchor protein (LRBA)

Lipopolysaccharide-responsive and beige-like anchor protein (LRBA) is a large, cytoplasmic scaffolding/adaptor protein encoded by the LRBA gene and contains various functional domains including BEACH, PH, and WD40 repeats[1][3][6]. LRBA is essential for vesicle trafficking, membrane receptor recycling (especially in immune cells), and immune regulation, and it plays a fundamental role in autophagy, apoptosis, and maintaining homeostasis of plasma membrane receptors[1][6]. LRBA regulates re-shuttling of CTLA4, a key T-cell co-inhibitory receptor, to the plasma membrane, and its deficiency results in loss of CTLA4 surface expression, contributing to immune dysregulation and autoimmunity[6]. Mutations of LRBA cause severe immune deficiencies such as common variable immunodeficiency (CVID), characterized by low immunoglobulin levels, B cell defects, increased risk of autoimmunity, and inflammations[1][2]. LRBA overexpression has been observed in several cancers, and its molecular interactions include EGFR, Notch, PKA, Ras, and p53 signaling pathways[1]. LRBA expression is widespread, seen in multiple organs and cell types including immune cells, neurons, and epithelial tissues[2][4]. The therapeutic management of LRBA deficiency often includes immune modulators (e.g., abatacept, IVIG), and testing for protein or CTLA4 levels can serve as biomarkers[7]. Safety concerns in LRBA-targeted therapy or deficiency include increased infection risk, autoimmunity, and challenges in immune regulation[1][6].

Other names

Beige-like proteinCDC4-like proteinBGLCDC4LCVID8LAB300LBAuc.147

Restoration of CTLA4 surface expression (for CTLA4 pathway drugs in LRBA deficiency)