MZB1 (marginal zone B and B1 cell specific protein) is an endoplasmic reticulum-resident chaperone protein that plays crucial roles in B cell function and immunoglobulin production. Primarily, MZB1 facilitates the assembly and secretion of polymeric IgM and dimeric IgA by interacting with their heavy chain tail pieces 12. The protein undergoes post-translational regulation through citrullination by peptidylarginine deiminase 2 (PAD2), which enhances its interaction with immunoglobulins and promotes IgM/IgA secretion 1. MZB1 is predominantly expressed in plasma cells, marginal zone B cells, and B1 cells, where it serves as a co-chaperone in antibody folding and maintains calcium homeostasis between the ER and cytoplasm 3. Disease relevance includes significant upregulation in chr5 rhinosinusitis with nasal polyps, where MZB1-expressing cells drive local IgE overproduction 4. Conversely, MZB1 deficiency increases colorectal cancer susceptibility through reduced intestinal IgA levels and altered gut microbiota 2. In periodontitis, MZB1 inhibits periodontal ligament cell migration via NF-κB signaling, promoting alveolar bone loss 5. Clinically, MZB1 dysregulation is implicated in multiple pathological conditions including autoimmune diseases, cancer progression, and inflammatory disorders, positioning it as a potential therapeutic target 36.