Unveiling the multifaceted role of MZB1 in health and disease toward potential therapeutics. A comprehensive review.

Marginal zone B and B1 cell specific protein (MZB1), initially identified as a proapoptotic caspase-2 and caspase-9-binding protein, has emerged as a critical regulator of diverse cellular processes. MZB1 plays a pivotal role in immune cell differentiation and functions as a co-chaperone involved in integrin activation, antibody folding, and secretion. It also regulates calcium flux between the endoplasmic reticulum (ER) and cytoplasm, maintaining calcium in the ER to keep an oxidizing environment. Depletion of MZB1 disrupts calcium homeostasis, elevating cytosolic calcium and activating downstream signaling pathways. Moreover, the discovery of five distinct isoforms of MZB1, each with its own specific functional roles, underscores the complexity of its involvement in cellular activities. MZB1 dysregulation has been implicated in diverse pathological conditions, including cancer, obesity, immune responses, inflammation, and autoimmune diseases. Notably, proteomic and functional studies have revealed that upregulated MZB1 contributes to multiple myeloma progression. Elevated MZB1 expression is associated with poor prognosis in CLL and demonstrates prognostic potential in DLBCL. This review explores the multifaceted functions of MZB1 and highlights the necessity for continued research into its isoforms and molecular mechanisms, particularly in the context of diagnostic and therapeutic interventions.