B-lymphocyte antigen CD19 is a single-pass type I transmembrane glycoprotein of the immunoglobulin superfamily. It consists of two Ig-like C2-type domains, and is expressed on follicular dendritic cells and B cells. CD19 acts as a co-receptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes. It is required for mature B cell responsiveness to antigen stimulation, germinal center development, and antibody affinity maturation, but not necessary for early stages of B cell differentiation in the bone marrow. CD19 associates with various molecules including BCR, CD81, CD38, CD21, CD22, and IFITM1/CD225/Leu-13, to amplify B cell signaling and lower the threshold for antigen stimulation through the BCR. It initiates signaling pathways that lead to phosphatidylinositol 3-kinase activation and intracellular Ca²⁺ store mobilization. CD19 polymorphisms and up-regulation can lead to the development of autoimmunity by promoting autoantibody production. Mutations in it are associated with severe immunodeficiency syndromes characterized by diminished antibody production. CD19 has emerged as a promising therapeutic target for hematologic cancers and solid tumors, such as leukemias and lymphomas. Immunotherapy utilizing a chimeric antigen receptor (CAR) directed against it has also gained significant attention.