ACTL6B encodes a component of the neuron-specific chr7 remodeling BAF complex (nBAF) that plays critical roles in postmitotic neural development and dendrite formation 1. The protein functions in ATP-dependent chr7 remodeling by altering DNA-nucleosome topology to regulate gene transcription 1. During neural development, ACTL6B expression increases as neural progenitors differentiate into neurons, where it becomes essential for dendrite development and neuronal maturation 1. The nBAF complex containing ACTL6B normally represses early response genes, and loss of ACTL6B function leads to inappropriate activation of AP1 transcription factors and disrupted chr7 accessibility 2. Recent evidence suggests ACTL6B also functions in the nucleolus where it plays a crucial role in ribosome biogenesis, particularly pre-rRNA processing, expanding its role beyond chr7 remodeling 3. Pathogenic variants in ACTL6B cause two distinct disorders: biallelic loss-of-function mutations lead to severe developmental and epileptic encephalopathy 76 (DEE76) with profound intellectual disability, intractable seizures, and brain abnormalities 45, while de novo heterozygous mutations cause a milder autosomal dominant disorder with moderate intellectual disability and speech deficits 13. Patient-derived neurons demonstrate impaired dendrite development, dysregulated gene expression, and neuronal hyperexcitability 16.