Given its pivotal involvement in B-cell homeostasis, and beyond its extensively documented role in B-cell lymphoproliferative disorders (Du et al, 2019; Kaiser et al, 2021), CXCR4 can play a contributory role, if not a central one, in non-malignant B-cell disorders, ranging from immunodeficiencies to autoimmune diseases. This evidence concerns the gene CXCR4 and immunodeficiency disease.