Human BAFF (B cell–Activating Factor), also known as BLyS or TNFSF13B, is a member of the tumor necrosis factor (TNF) superfamily and is a critical regulator of B cell development, survival, and humoral immunity. BAFF is produced primarily by monocytes, macrophages, dendritic cells, neutrophils, and certain stromal and epithelial cells, and it signals through the receptors BAFF-R (TNFRSF13C), TACI (TNFRSF13B), and BCMA (TNFRSF17) to promote transitional and mature B cell survival, immunoglobulin class switching, and the maintenance of long-lived plasma cells. In healthy individuals, BAFF supports normal antibody production and immune homeostasis; however, elevated BAFF levels can drive excessive B cell activation and autoantibody production. Dysregulated BAFF signaling has been strongly implicated in autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjögren’s syndrome, and multiple sclerosis, as well as in B cell malignancies including multiple myeloma and certain lymphomas. Therapeutic targeting of BAFF (e.g., with belimumab) has demonstrated clinical benefit in autoimmune disease, highlighting its importance in immune regulation. In clinical and translational research, human BAFF serves as a key biomarker and therapeutic target for modulating B cell–mediated immunity and antibody-driven pathology.