KCTD15 is a multifunctional protein that serves as a transcriptional corepressor and regulator of diverse developmental processes. Its primary function involves inhibiting AP2 transcriptional activity through interaction with its activation domain 1. During embryonic development, KCTD15 plays critical roles in neural crest formation and ectodermal development, forming multimeric complexes with KCTD1 that can compensate for each other's loss 2. The protein regulates the NF-κB signaling pathway, with its upregulation associated with increased pIKK-β and pIκB-α levels in various physiological and pathological contexts 3. KCTD15 is significantly involved in metabolic regulation, particularly fat deposition and adipogenesis. It shows differential expression during adipocyte differentiation and is targeted by miR-381, which promotes adipogenesis by downregulating KCTD15 expression 4. Genetic variants in KCTD15 are associated with obesity, body mass index, and type 2 diabetes risk across multiple populations 5. Disease relevance includes aplasia cutis congenita, where KCTD1/KCTD15 dysfunction in neural crest cells causes midline skull defects 2, eating disorders particularly bulimia nervosa 6, and potential involvement in PFAS-mediated polycystic ovary syndrome pathogenesis 7. Clinical significance encompasses metabolic disorders, neurodevelopmental conditions, and reproductive health.