Plexin-D1 (PLXND1)

Plexin-D1 is a single-pass type I transmembrane receptor belonging to the plexin family that primarily mediates signaling for class 3 semaphorins, such as Semaphorin 3E (Sema3E) [1, 4, 8]. It is essential for embryonic development, specifically in guiding axonal growth and patterning the vascular system [1, 5]. While its expression is low in most adult tissues, it is significantly upregulated in various malignancies, including prostate, breast, and colon cancers, where it promotes tumor angiogenesis, metastasis, and lineage plasticity [4, 10, 12]. Plexin-D1 also functions as an endothelial mechanosensor in cardiovascular diseases like atherosclerosis and is involved in immune responses such as germinal center formation [7, 9, 11]. In certain neuropathic pain conditions, it has been identified as a target for autoantibodies that increase neuronal membrane permeability [17, 20]. Therapeutic approaches under investigation include monoclonal antibodies, antibody-drug conjugates (ADCs), and peptide inhibitors like D1SP, which aim to inhibit pathological signaling or deliver targeted therapy to the tumor microenvironment [6, 10].

Other names

PLXND1PLEXD1Plexin D1

Antagonism of semaphorin-plexin signaling, targeted delivery of cytotoxic payloads via antibody-drug conjugates, and decoy receptor-mediated ligand sequestration.