CNIH4 (cornichon family AMPA receptor auxiliary protein 4) is an endoplasmic reticulum (ER) membrane protein that serves as a cargo-sorting receptor for G protein-coupled receptors (GPCRs) trafficking from the ER to the cell surface 1. The protein functions by interacting with newly synthesized GPCRs and controlling their export from the ER through interaction with the COPII coat complex machinery, specifically co-immunoprecipitating with Sec23 and Sec24 components 1. Beyond its trafficking role, CNIH4 has emerged as an important oncogenic factor in multiple cancers. In cervical cancer, it promotes cell survival and progression by inhibiting ferroptosis through upregulation of SLC7A11-mediated cystine import and glutathione synthesis 2. In hepatocellular carcinoma, CNIH4 amplifies TGFα secretion, activating EGFR and downstream pAKT/pERK signaling pathways 3. The protein also regulates glioma stem cell-like properties and chemotherapy sensitivity 4. Clinically, CNIH4 overexpression correlates with poor prognosis across multiple cancer types including cervical, gastric, and hepatocellular carcinomas 567. Interestingly, in epilepsy, genetic variants in the CNIH4 locus are protective against drug-resistant focal epilepsy 8, suggesting tissue-specific functional roles.