TNFRSF16/NGF Receptor/CD271

TNFRSF16/NGF receptor/CD271, also called p75NTR, is a pan-neurotrophin receptor that regulates cell death, survival, differentiation, axon elongation, and cell-cycle control^[1][2]. Mechanistically, ligand and co-receptor context shape p75NTR signaling through its intracellular death domain, regulated proteolysis, NF-κB, JNK, RIP2, RhoGDI, and Shc-related TrkA signal augmentation^[3][4][5][6]. In disease models, ischemic stroke induces astrocytic and endothelial p75NTR expression, while p75NTR knockdown or LM11A-31 inhibition reduces BBB leakage, NF-κB/HIF-1α activation, MMP-9, VEGF, leukocyte infiltration, and brain injury^[7]. In cancer models, CD271 marks tumor-initiating cells in head and neck squamous cell carcinoma, and p75NTR/CD271-mediated glioma invasion requires regulated interaction with PDLIM1^[8][9]. Compared with related p75NTR isoforms, complete exon IV deletion prevents expression of both full-length and shorter p75NTR isoforms and increases basal forebrain cholinergic neuron numbers more strongly than partial exon III mutation^[10]. For experimental applications, BNN27 activates p75NTR-dependent neuronal survival signaling, whereas small-molecule p75NTR inhibitors support target validation in neurodegeneration and ischemic injury models^[6][11].