NTRK2

NTRK2, or neurotrophic receptor tyrosine kinase 2, encodes the TrkB receptor, a high-affinity receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). TrkB is a member of the tropomyosin receptor kinase family and plays a central role in neurotrophin signaling that supports neuronal survival, development, and synaptic plasticity.

The TrkB protein is a single-pass transmembrane receptor with an extracellular ligand-binding domain, a transmembrane segment, and an intracellular tyrosine kinase domain. Binding of BDNF or NT-4 induces receptor dimerization and autophosphorylation on multiple tyrosine residues, creating docking sites for downstream signaling molecules and adaptor proteins.

Activated TrkB triggers several signaling pathways, including PI3K-AKT, Ras-MAPK-ERK, and PLCγ-Ca2+. These pathways promote neuronal survival and differentiation, regulate synaptic development and plasticity, and influence learning, memory, mood, and energy balance. TrkB signaling also modulates synaptic transmission and long-term changes in synaptic strength.

NTRK2 expression is widespread in the central nervous system, with notable presence in regions such as the cortex and hippocampus. Dysregulation of TrkB signaling has been studied in various neurological and psychiatric contexts. Clinically, the most established relevance of NTRK2 involves rare gene fusions involving NTRK2 in tumors, which can be targeted by TRK inhibitors (e.g., larotrectinib, entrectinib) regardless of tumor histology. Ongoing research continues to clarify NTRK2’s broader roles in health and disease.