Human BAFF receptor (BAFF-R), also known as TNFRSF13C or CD268, is a member of the tumor necrosis factor receptor (TNFR) superfamily and serves as the primary receptor for BAFF (B cell–Activating Factor/BLyS). BAFF-R is expressed predominantly on transitional and mature naïve B cells, with lower expression on memory B cells and minimal expression on plasma cells. Engagement of BAFF-R by BAFF activates key intracellular signaling pathways, particularly the non-canonical NF-κB pathway, promoting B cell survival, maturation, metabolic fitness, and peripheral B cell homeostasis. BAFF-R signaling is essential for the maintenance of the mature B cell compartment; genetic deficiency or functional impairment of BAFF-R results in reduced peripheral B cell numbers and impaired antibody responses. Conversely, excessive BAFF–BAFF-R signaling contributes to pathological B cell survival and autoantibody production. Dysregulation of BAFF-R signaling has been implicated in autoimmune diseases such as systemic lupus erythematosus (SLE), Sjögren’s syndrome, and rheumatoid arthritis, as well as in B cell malignancies including chronic lymphocytic leukemia (CLL) and certain lymphomas. In clinical and translational research, human BAFF-R is studied as a key regulator of B cell–mediated immunity and as a therapeutic target for modulating pathological B cell survival and antibody-driven disease.