NETO proteins are auxiliary subunits that play crucial roles in modulating the biophysical properties of Kainate receptors (KARs) and N-methyl-D-aspartate receptors (NMDARs).  NETO proteins modulate these receptors both in vivo and in vitro. NETO1 is also responsible for the slow kinetics of postsynaptic KAR-mediated currents and regulate synaptic recruitment of Kainate receptors¹.

NETO1 is a single transmembrane domain protein containing two extracellular CUB domains of about 110 amino acids, a low-density lipoprotein receptor domain, and a cytoplasmic tail of almost 167 amino acids that includes a C-terminal TRV class I PDZ binding motif²_.

NETO1 and NETO2, are highly homologous, but have a different expression patterns and distinct functional effects. NETO1 subunit is expressed in high levels in the developing hippocampus and regulates axonal and presynaptic Kainate receptors at the CA3-CA1 region of the hippocampus. NETO1 deficiency resulted in impairs synaptogenesis and disrupts synchronization of the CA3-CA1 neuronal populations^1,3. NETO1 is enriched in the post-synaptic density where it co-localizes with post-synaptic density-95 (PSD-95) and GluN1².