The molecular details for the glutamate receptor channel mediated and modulated fast signal transmission in for the sensory input in the peripheral nervous system is well established. However, in the most recent years several new classes of endogenous membrane proteins were described as important interactors for structurally related, ligand gated ion channels of AMPA, Kainate and NMDA receptor subtypes. Some of the auxiliary subunit are expected to be important endogenous regulators for glutamate receptor channel function in the central as well as the peripheral nervous system. About ten year ago Lynx-1 was described as endogenous GPI anchored, prototoxin modulating the response of the nicotinic acetylcholine receptors (nAChR). In absence of Lynx-1 the EC50 of the nAChR for nicotine was decreased by 10-fold, receptor desensitization was reduced but synaptic efficiency was enhanced. For ligand gated glutamate receptors we recently identified a similar, prototoxin like membrane bound protein (Cystine-knot AMPA receptor modifying protein; CKAMP), which is, however, not sequence related to Lynx-1 or any other member of the Ly6/plaur domain protein family. This novel CKAMP has a single membrane spanning domain and when co-expressed with AMPA receptors in Xenopus oocytes, AMPA receptor currents are strongly reduced. In an exhausted data base search we found three additional members of the CKAMP protein family. All four CKAMP members are exclusively expressed in the brain, in different brain regions. The N-terminal, extracellular part of the protein contains a Cys-knot motif. A very similar pattern of Cystines can be found in conotoxins of the O-superfamily, which might be taken as indication that CKAMP reflect the Lynx analogs of AMPA receptors. The physiological functions of CKAMPs, their relation to other auxiliary subunits of glutamate receptor and their therapeutic potential will be discussed.