PLXNC1 (plexin C1) is a transmembrane receptor that mediates cellular responses to semaphorin ligands, particularly SEMA7A 1. Upon semaphorin binding, PLXNC1 triggers cytoskeletal rearrangement and cytokine secretion including IL-6 and IL-8. The receptor plays dual roles in pathological processes: in gastric cancer, PLXNC1 promotes tumor cell proliferation and facilitates M2 macrophage polarization through exosomal miR-92b-5p transfer, with STAT3 transcriptionally regulating PLXNC1 expression 2. In osteoarthritis, PLXNC1 mediates inflammatory injury and extracellular matrix degradation in IL-1β-exposed chondrocytes via GRP78 interaction 3. PLXNC1 also participates in spinal cord injury neuroinflammation through ferroptosis-related pathways 4 and testicular homeostasis by upregulating the SEMA7A/PLXNC1 inflammatory pathway while downregulating metabolic signaling 5. Conversely, genetic studies identify PLXNC1 as negatively correlated with keloid formation 6 and as a potential prognostic marker in primary mediastinal B-cell lymphoma 7. PLXNC1 emerges as a multi-functional immune regulator with therapeutic potential across inflammatory, fibrotic, and neoplastic diseases.