TNFRSF13B (TACI) is a TNF receptor superfamily member functioning as a B-cell-specific receptor that binds BAFF (TNFSF13B) and APRIL (TNFSF13) ligands with high affinity 1. It mediates calcineurin-dependent NF-AT activation and NF-κB/AP-1 signaling pathways, regulating B and T-cell function and humoral immunity. TNFRSF13B mutations are significantly associated with primary antibody deficiencies: biallelic mutations cause hypogammaglobulinemia and common variable immunodeficiency (CVID), while monoallelic variants increase disease risk (relative risk 3.6) and influence clinical presentation including lymphadenopathy, granulomata, and autoimmune complications 21. The C104R variant represents the most common pathogenic mutation 1. Beyond immunodeficiency, TNFRSF13B variants contribute to IgA nephropathy pathogenesis as identified in genome-wide association studies 3. In inflammatory contexts, TNFRSF13B-expressing B cells respond to neutrophil-derived BAFF in hidradenitis suppurativa lesions, supporting B-cell persistence and function 4. Notably, gain-of-function variants at TNFRSF13B increase multiple myeloma risk through amplified B-cell responses, contrasting with loss-of-function immunodeficiency mechanisms 5. TNFRSF13B genetic testing aids diagnosis of antibody deficiencies, though variant interpretation complexity limits immediate clinical management impact 2.