CD72 is a B-cell co-receptor with dual regulatory roles in BCR signaling and immune homeostasis. As a C-type lectin superfamily member expressed from pro-B through mature B cells 1, CD72 functions as a negative regulator of B-cell responsiveness through its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs, which recruit the tyrosine phosphatase SHP-1 to inhibit BCR signaling 21. CD72 recognizes Sm/ribonucleoprotein self-antigens and can bind semaphorin 4D (CD100) as a natural ligand 23. CD72 also serves as a ligand for CD5, maintaining regulatory T and B-cell homeostasis. A splice variant lacking exon 8 (CD72Δex8) localizes to the endoplasmic reticulum and is associated with SLE resistance, regulating antibody production 4. In disease contexts, CD72 emerges as a therapeutic target in B-cell malignancies. Humanized anti-CD72 nanobody CAR-T cells demonstrate enhanced potency against CD19-refractory B-ALL and B-cell lymphomas, with the H24 clone showing particular promise for clinical translation 56. Conversely, CD72-positive macrophages driven by Rel transcription factor promote pro-inflammatory cardiac injury in heart failure, suggesting CD72+ cells as cardiovascular therapeutic targets 7.