Research has shown that activation of the TrkB receptor can lead to down regulation of the KCC2 chloride transporter in cells of the CNS.

The full-length isoform (TK+) is a typical tyrosine kinase receptor, and transduces the BDNF signal via Ras-ERK, PI3K, and PLCγ.

A number of Trk inhibitors are (in 2015) in clinical trials and have shown early promise in shrinking human tumors.

[16] TrkB and its ligand BDNF have been associated to both normal brain function and in the pathology and progression of Alzheimer's disease (AD) and other neurodegenerative disorders.

[19] Both TrkB and BDNF are downregulated in the brain of early AD patients with mild cognitive impairments,[20][21] while work in mice has shown that reducing TrkB levels in the brain of AD mouse models leads to a significant increase in memory deficits.

[22] In addition, combining the induction of adult hippocampal neurogenesis and increasing BDNF levels lead to an improved cognition, mimicking exercise benefits in AD mouse models.

[23] The effect of TrkB/BDNF signalling on AD pathology has been shown to be in part mediated by an increase in δ-secretase levels, via an upregulation of the JAK2/STAT3 pathway and C/EBPβ downstream of TrkB.