Plexin B2 is a 240 kD transmembrane receptor belonging to the semaphorin receptor family, B subfamily. All the family members share an extracellular semaphorin domain and an intracellular plexin domain-containing tail that can mediate intracellular signaling. Distinct from the other subfamily members, Plexin B2 contains an intracellular domain with a PDZ motif (post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (DlgA), and zonula occludens-1 protein (zo-1)), which can relay extracellular signals to intracellular motifs. Similar to the other B family members, Plexin B2 was also originally found in the nervous system and was later reported on endocrine, reproductive, urinary, digestive, respiratory, and immune systems. In immune cells, Plexin B2 is highly expressed on macrophages, conventional dendritic cells (cDCs), and plasmacytoid dendritic cells (pDCs). It is also expressed on T cells and T-dependent germinal center B cells. Plexin B2 facilitates ligand induced cell guidance and migration in the nervous system, and induces cytoskeletal changes in overexpression assays through RhoGTPase. However, the function of Plexin B2 in the immune system is not conclusive. Plexin B2 has been reported to modulate upon activation of DCs by TLR ligands, TNF-alpha, and anti-CD40. It also functions as a negative regulator of Rac and Cdc42 and modulates cell motility in macrophages. Plexin B2 has been found to have several semaphorin ligands including Semaphorin-3E, Semaphorin-4A, Semaphorin-4C, and Semaphorin-4D.