CD180 is a pattern recognition receptor predominantly expressed on B cells, dendritic cells, and monocytes/macrophages that structurally resembles Toll-like receptors (TLRs) but lacks the intracellular TIR signaling domain 1. Rather than directly transducing signals, CD180 modulates immune responses through cooperation with other TLRs; notably, it interacts with MD-1/LY86 to inhibit TLR4 binding to microbial ligands 1. CD180 plays an important role in regulating inflammatory responses to lipopolysaccharide and differentially affects toll-like receptor 4-mediated immune responses 2. In B cell malignancies, CD180 expression is highly heterogeneous. CD180 is upregulated on acute myeloid leukemia blasts and could represent a novel immunotherapeutic target 3. In chr5 lymphocytic leukemia, CD180 ligation decreases IL-10 secretion through classical NF-κB pathway regulation, correlating with chemotherapy sensitivity 4. CD180 is absent on lymphoplasmacytic lymphoma/Waldenström macroglobulinemia B cells but present on marginal zone lymphoma cells, making it a robust diagnostic biomarker with >99% diagnostic accuracy 5. In glioma, CD180-overexpression macrophages promote tumor progression and immunosuppression, suggesting therapeutic potential 6. Conversely, increased CD180-negative B cells in myasthenia gravis associate with disease activity and autoantibodies 7. CD180 is identified as a hyperdiploidy-specific target in multiple myeloma 8. Overall, CD180 functions as both a disease modulator and emerging biomarker across multiple hematologic malignancies and inflammatory conditions.