AFF3 (ALF transcription elongation factor 3) is a transcriptional regulator that functions as a component of the super elongation complex, controlling gene expression during development and cellular processes 1. The protein regulates transcription elongation and serves as a transcription coregulator with roles in neurogenesis and development 1. AFF3 demonstrates complex dosage sensitivity, where both loss-of-function and gain-of-function variants cause distinct pathological effects 2. De novo variants in AFF3's degron region cause KINSSHIP syndrome, characterized by intellectual disability, mesomelic dysplasia, horseshoe kidney, and seizures 1. Additionally, CGG repeat expansions in AFF3's promoter are associated with neurodevelopmental disorders and reduced educational attainment 3. In cancer contexts, AFF3 functions as a tumor suppressor in prostate cancer by regulating ferroptosis sensitivity through ACSL4 downregulation 4, while also serving as an eQTL-mediated susceptibility gene in renal cancer 5. The protein participates in immune regulation, as β-catenin/AFF3 downregulation affects immune cell recruitment in liver metastasis 6. These findings demonstrate AFF3's critical roles in development, neurological function, and cancer progression through transcriptional control mechanisms.