LRBA, the lipopolysaccharide-responsive and beige-like anchor protein, is a cytoplasmic protein ubiquitously distributed [4]. It is involved in multiple biological processes, including vesicular trafficking, autophagy, and apoptosis [2]. In the immune system, it is thought to regulate CTLA4, a potent inhibitory immune receptor, playing a key role in immune responses [1].

In Lrba knockout mice, defective AQP2 trafficking was observed, leading to low urinary concentrating ability as LRBA-PKA complex at the recycling endosome facilitated AQP2 phosphorylation in response to vasopressin [5,6]. In humans, LRBA deficiency, caused by bi-allelic mutations, results in a primary immunodeficiency with various clinical features such as hypogammaglobulinemia, lymphoproliferative syndrome, inflammatory bowel disease, and autoimmune manifestations [2]. Patients with LRBA deficiency show CTLA4 loss and immune dysregulation, which can be responsive to abatacept therapy [1,3].

In conclusion, LRBA is essential for processes like urinary concentration and body water homeostasis through its role in AQP2 regulation. In the immune system, it is crucial for maintaining immune balance by regulating CTLA4. The study of Lrba knockout models and human cases of LRBA deficiency has provided insights into its functions and its implications in immunodeficiency and autoimmune diseases.