CNIH2 is an auxiliary protein that regulates AMPA receptor (AMPAR) trafficking and gating properties. It promotes AMPAR targeting to the cell membrane and synapses while modulating their activation, deactivation, and desensitization rates 1. Structurally, CNIH2 destabilizes the desensitized state of AMPAR complexes and stabilizes polyamine binding to the ion channel selectivity filter, while attenuating polyamine block and reducing antiepileptic drug potency 2. CNIH2 enhances AMPAR tetramerization through transmembrane domain interactions, facilitating receptor biogenesis and surface expression more effectively than other auxiliary subunits 3. Beyond synaptic function, CNIH2 serves as a COPII cargo receptor in the secretory pathway, promoting trafficking of proteins through ER-Golgi compartments 4. Pathologically, elevated CNIH2 expression is associated with poor prognosis in esophageal squamous cell carcinoma and prostate cancer. In esophageal cancer, CPSF3-mediated alternative polyadenylation increases CNIH2 expression by eliminating miR-125a-5p binding sites, promoting tumor progression 5. Conversely, knockdown of CNIH2 in prostate cancer cells inhibits proliferation, migration, and invasion, with low CNIH2 expression correlating with improved progression-free survival 6. These findings establish CNIH2 as both a critical synaptic regulator and potential oncogenic driver in specific cancer contexts.