MS4A4A is a tetraspan transmembrane protein selectively expressed by macrophages and microglial cells that plays critical roles in immune regulation and cellular signaling 1. The protein is induced during monocyte-to-macrophage differentiation and is associated with M2/M2-like macrophage polarization 1. MS4A4A localizes to lipid rafts where it interacts with the β-glucan receptor dectin-1, facilitating dectin-1-dependent signaling and production of effector molecules 1. In cancer contexts, MS4A4A is highly expressed in tumor-associated macrophages (TAMs) and promotes M2 polarization through activation of PI3K/AKT and JAK/STAT6 pathways 2. High MS4A4A expression correlates with poor prognosis across multiple cancer types and immunosuppressive tumor microenvironments 23. Targeting MS4A4A with monoclonal antibodies reduces M2-TAM infiltration, enhances CD8+ T-cell responses, and improves immunotherapy efficacy 24. In neurological contexts, microglial MS4A4A supports phagocytic activity and protects against epileptic seizures in Alzheimer's disease by maintaining calcium influx and mitochondrial fitness 5. The protein also correlates with synovial inflammation in rheumatoid arthritis and can counteract corticosteroid responses 6.