Neuropilin and tolloid-like protein 2 (NETO2)

Neuropilin and tolloid-like protein 2 (NETO2) is a **brain-specific single-pass transmembrane protein** that functions as an **auxiliary subunit for kainate-type ionotropic glutamate receptors** and as a key **regulator of excitatory neurotransmission**[1][5][7]. NETO2 modulates the kinetics and synaptic localization of kainate receptors, controls neuronal chloride homeostasis by interacting with the KCC2 transporter, and influences the stability of glutamate receptor–scaffold complexes[2][5]. In the central nervous system, it is important for maintaining synaptic inhibition and regulating neuronal signaling[2][7]. In oncology, aberrant expression of NETO2 has been linked to tumor progression, invasion, and metastasis (notably in gastric cancer), acting through pathways such as PI3K/AKT/NF-κB/Snail and promoting epithelial–mesenchymal transition[4]. NETO2 is of growing interest as a disease biomarker and potential therapeutic target especially in cancers, but its essential synaptic regulatory roles suggest targeting must be approached with care to avoid detrimental effects on neuronal function.

Other names

NETO2Neuropilin and tolloid-like protein 2BTCL2UNQ1926/PRO4401FLJ10430NEOT2Brain-specific transmembrane protein containing 2 CUB and 1 LDL-receptor class A domains protein 2Neuropilin (NRP) and tolloid (TLL)-like 2

Not applicable (no approved or experimental drugs known to target NETO2 directly in the literature; functions mainly as a regulatory auxiliary subunit or scaffolding protein)