TNFRSF13C encodes BAFF receptor (BAFFR), a pro-survival receptor predominantly expressed on B cells that binds the TNF family ligand BAFF (TNFSF13B) 1. BAFFR is critical for B cell development, promoting survival of transitional and mature B cells and supporting the overall B cell response 2. Mechanistically, BAFFR engagement provides survival signals that prevent apoptosis of developing B lymphocytes, with particular importance at the immature-to-transitional B cell developmental checkpoint 1. Clinically, homozygous TNFRSF13C deletions cause severe immunodeficiency characterized by B lymphopenia, agammaglobulinemia, and impaired humoral immunity, though IgA production can remain relatively preserved 1. Conversely, elevated BAFF levels drive autoimmunity by expanding autoreactive B cell populations 2. TNFRSF13C mutations associate with common variable immunodeficiency 3. Therapeutically, BAFFR-targeted therapies like ianalumab induce sustained B cell depletion and show benefits in autoimmune diseases including primary Sjögren's syndrome and systemic lupus erythematosus 45. Additionally, TNFRSF13C expression serves as a marker of functional tertiary lymphoid structures in cholangiocarcinoma, correlating with improved immunotherapy response and prognosis 6.