Transmembrane AMPA receptor regulatory protein gamma-8 (TARP γ-8)

Transmembrane AMPA receptor regulatory protein gamma-8 (TARP γ-8), encoded by the *CACNG8* gene, is a claudin-like, four-pass transmembrane auxiliary subunit that modulates the function of AMPA-type glutamate receptors (AMPARs) in the central nervous system. TARP γ-8 controls the trafficking of AMPA receptors to synaptic membranes and fine-tunes their gating kinetics, pharmacology, and synaptic localization[2][7][9]. It is especially enriched in the hippocampus and select cortical areas, where it alters channel conductance, desensitization, and drug sensitivity of AMPA receptors[5][7]. TARP γ-8 is now recognized as a valid drug target for neurological diseases such as epilepsy, with specific negative allosteric modulators (e.g., JNJ-059, LY3130481) showing promise in selectively dampening excitatory neurotransmission mediated by γ8-containing AMPAR complexes[5]. Altered expression or function of TARP γ-8 is implicated in neuropsychiatric conditions such as schizophrenia[6] and potentially in broader CNS pathologies associated with glutamatergic dysregulation.

Other names

TARP gamma-8Gamma-8 (γ-8)CACNG8 (gene name)Transmembrane AMPA receptor regulatory protein γ8

Allosteric modulation of AMPA receptors via auxiliary subunit binding[5][3] Negative allosteric modulation (e.g., JNJ-059 and LY3130481 reduce AMPA receptor-mediated currents by stabilizing inactive conformations when bound to γ8-containing complexes)[5] Enhancement or reduction of receptor trafficking to synaptic membranes[6]