TrkB

TrkB (tropomyosin receptor kinase B), encoded by NTRK2, is a neurotrophic tyrosine kinase receptor that mediates the cellular actions of brain-derived neurotrophic factor (BDNF) and contributes to neuronal differentiation, neuroplasticity, and homeostasis^[1][2]. Mechanistically, ligand-induced activation of full-length TrkB (TrkB.FL) triggers receptor autophosphorylation and engages intracellular signaling pathways including PI3K, MAPK/ERK, and PLCγ, thereby supporting neurotrophic responses and synaptic function^[3][4]. Alternative splicing of NTRK2 generates distinct receptor isoforms, including TrkB.FL and truncated variants such as TrkB.T1, TrkB.T2, and TrkB-T-ShC, which lack the tyrosine kinase domain and therefore differ fundamentally in signaling capacity^[5][6]. Compared with TrkB.FL, TrkB.T1 is the major truncated isoform in the adult brain and can negatively regulate full-length receptor signaling through dominant-inhibitory mechanisms while also exhibiting independent biological activities^[6][7][8]. Altered TrkB isoform balance has been associated with neurodegeneration, ischemic injury, amyotrophic lateral sclerosis, spinal muscular atrophy, psychiatric disorders, and cognitive dysfunction, highlighting the importance of isoform-specific regulation in disease biology^{[2][9][10][11]}. In experimental systems, modulation of BDNF-TrkB signaling and manipulation of TrkB isoform expression are widely used to investigate neuronal survival, differentiation, synaptic plasticity, and disease mechanisms, making TrkB a valuable target for mechanistic and translational neuroscience research^[3][6][10].