CD22 (also known as siglec-2) is a member of the sialic acid-binding immunoglobulin-type lectin (Siglec) family of immunomodulatory receptors. CD22 can bind to its ligand ? 2,6-linked sialic acid on different cells (trans interaction) as well as on the same cells (cis interaction). CD22 is predominantly expressed on B cells and functions as an inhibitory co-receptor for the B cell receptor (BCR). After BCR ligation, the tyrosine kinase Lyn is activated and phosphorylates two distal of the four ITIM motifs in the intracellular carboxy-terminal region of CD22, which then recruit tyrosine phosphatases, including SHP-1, to the plasma membrane, and in turn, they get tyrosine-phosphorylated and activated to damp the signaling pathways initiated by BCR ligation. CD22 has been actively pursued as a therapeutic target for autoimmune diseases. Due to almost exclusive expression on B cells, it is also actively pursued as a therapeutic target for multiple B cell malignancies.