KCTD10 functions as a substrate-recognition adapter of CUL3-based E3 ubiquitin-protein ligase complexes 1, mediating ubiquitination and proteasomal degradation of multiple target proteins. It serves dual roles in cellular homeostasis: regulating ferroptosis sensitivity through SLC7A11 degradation 1, and controlling genome stability by sensing transcription-replication conflicts, where it bridges the replisome and RNA polymerase machinery to facilitate bypass of colliding polymerases through TCEA2 ubiquitination 2. KCTD10 undergoes liquid-liquid phase separation to regulate postsynaptic Rho protein (RHOB) accumulation, affecting synaptic architecture and neuronal function 3. During brain development, KCTD10 expression in neuronal progenitors regulates cortical layer specification through KCTD13 degradation 4. In lung cancer, KCTD10 suppresses metastasis and angiogenesis by targeting β-catenin for K48-linked ubiquitination, reducing PD-L1 expression and improving anti-PD-1 immunotherapy efficacy 5. KCTD10 also regulates coronary atherosclerosis progression through immune cell modulation 6. Expression is controlled by transcription factors SP1 and AP-2alpha at the promoter 7. Genetic variants in KCTD10 (rs56209061) associate with reduced age-related macular degeneration risk 8, and rare de novo mutations link to schizophrenia pathogenesis 3.