Immunoglobulin M (IgM), encoded by the IGHM gene, is a critical antibody class in the immune system. As the first antibody produced during an initial immune response, IgM serves as both a membrane-bound B-cell receptor (BCR) on naïve B cells and a secreted pentameric molecule. Its pentameric structure (five antibody units linked by a J chain) provides high avidity for antigen binding, enhancing pathogen neutralization and complement activation. The IGHM gene, located on chromosome 14 (14q32.33), undergoes V(D)J recombination during B-cell development to generate diverse antigen-binding regions. Membrane-bound IgM (monomeric) acts as a BCR, initiating signaling upon antigen recognition, while secreted IgM (pentameric) circulates in blood and lymph, playing a frontline role in early infection defense. Defects in IGHM are linked to agammaglobulinemia, a primary immunodeficiency marked by absent/reduced B cells and recurrent infections. Clinically, IgM levels are monitored in immune disorders, infections, and certain cancers (e.g., Waldenström’s macroglobulinemia). Its evolutionary conservation underscores its essential role in innate-like immunity, bridging early defense and adaptive immune activation. Research on IgM continues to inform vaccine design and therapies targeting B-cell dysfunction.