KCTD2 (potassium channel tetramerization domain containing 2) functions as a substrate adaptor protein for CUL3-RING E3 ubiquitin ligase complexes, regulating protein degradation through the ubiquitin-proteasome system 1. The protein forms hetero-oligomers with KCTD5 to recruit specific substrates, including the G-protein β-subunit (Gβ1/2), promoting its monoubiquitination at lysine-23 and regulating downstream G-protein signaling 1. KCTD2 also targets c-Myc for ubiquitin-mediated degradation, thereby suppressing cellular proliferation and stem cell characteristics 2. Along with related KCTD proteins (KCTD5, KCTD17), KCTD2 exhibits functional redundancy in controlling cellular growth, with combined knockout effects being most pronounced when all three isoforms are deleted 3. The protein localizes to synapses in neurons and appears evolutionarily conserved, as mouse KCTD2 can functionally substitute for Drosophila Insomniac in sleep regulation 4. Disease relevance includes associations with Alzheimer's disease risk 5, glioma suppression through c-Myc regulation 2, and potential cardiac abnormalities 6. KCTD2 expression changes have also been observed in osteoarthritis progression 7 and colorectal cancer metastasis 8.