Kainate receptors are less well understood than other members of the glutamate receptor family, and endogenous synaptic kainate receptors display certain properties that differ from heterologously expressed receptors. Particularly the slow decay of postsynaptic kainate receptors contrasts with the rapid deactivation and desensitization of receptors expressed in heterologous cells. We recently identified the neuropilin (NRP) and tolloid (TLL)-like protein (NETO2) as a novel accessory subunit of kainate receptors and showed that co expression of NETO2 with the kainate receptor subunit GluK2 slows both desensitization and deactivation, but does not affect receptor expression at the cell surface. Single-channel analysis showed that NETO2 also increases the open probability of kainate receptor channels, resulting in significantly larger peak glutamate-evoked currents. However, the kainate receptor family consists of five different subunits (GluK1-5) that can form homomeric and heteromeric receptors with different subunit compositions and functional properties. Here we tested if NETO2 modulation varies with subunit composition. Rapid application techniques were used to apply glutamate to outside-out patches that contained GluK1, GluK1/5 or GluK2/5 kainate receptors. As we found for GluK2 receptors, NETO2 also modulates these other recombinant kainate receptors. Co-expression of NETO2 slowed desensitization to varying degrees, and GluK1-containing receptors developed a second, very slow phase of decay. Interestingly, deactivation of heteromeric receptors containing GluK5 was also slowed by NETO2, an effect confirmed by measuring postsynaptic currents in neurons expressing recombinant kainate receptors. In addition, NETO2 markedly increased the rate at which both homomeric and heteromeric receptors recovered from desensitization The results suggest that NETO2 is a ubiquitous modulator of kainate receptors that has distinct effects that vary with subunit composition.