CACNG4 (calcium voltage-gated channel auxiliary subunit gamma 4) is a regulatory protein that modulates both calcium channels and glutamate receptors. The protein regulates L-type calcium channels containing CACNA1C subunits and controls trafficking and gating properties of AMPA-selective glutamate receptors, promoting their membrane targeting and modulating activation, deactivation, and desensitization rates 12. In cancer contexts, CACNG4 demonstrates significant pathological relevance. The gene is upregulated in various cancers including breast cancer, where its amplification at chromosome 17.1-24.2 correlates with poor prognosis and increased metastasis 3. CACNG4 promotes malignant transformation by closing calcium channel pores, inhibiting calcium influx, and altering survival pathway signaling involving AKT2, HDAC3, RASA1, and PKCζ 3. The protein appears to maintain calcium homeostasis in tumor cells, enhancing their survival and metastatic capacity 3. Clinically, CACNG4 serves as a potential biomarker across multiple cancer types, with upregulation observed in hepatocellular carcinoma stem cells 4, cervical intraepithelial neoplasia with viral coinfections 5, and breast cancer 6. The calcium channel inhibitor amlodipine shows therapeutic potential by targeting CACNG4-expressing cancer stem cells 4.