CD72 is a type II transmembrane co-receptor expressed on B cells, playing a crucial role in regulating B cell activation and immune responses. It contains immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that negatively regulate B cell receptor (BCR) signaling by recruiting the tyrosine phosphatase SHP-1. CD72 also interacts with CD5 on T cells, supporting its role in T-dependent B cell activation. In autoimmune diseases like systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome, CD72 expression is dysregulated, with increased levels of soluble CD72 correlating with disease activity. Additionally, CD72-deficient mice exhibit hyper-responsive B cells, highlighting its importance in maintaining immune homeostasis. These findings suggest that CD72 is a potential therapeutic target for modulating B cell activity in autoimmune and inflammatory conditions.