PHF21A (PHD finger protein 21A) is a histone-binding protein that functions as a component of the BHC (BRAF histone deacetylase) corepressor complex 1. As an unmethylated H3K4 reader, it associates with the histone demethylase LSD1 to regulate chr11 modifications and repress transcription of neuron-specific genes in non-neuronal cells 2. During neurodevelopment, PHF21A undergoes neuron-specific alternative splicing that precedes LSD1 splicing, resulting in stepwise deactivation of their complex and dampening excessive synaptogenesis 3. This microexon splicing attenuates PHF21A's nucleosome and DNA-binding capacity while the complex retains unique gene-regulatory roles through interactions with neuron-specific transcription factors and post-transcriptional processors 24. PHF21A is essential for cAMP-responsive gene expression pathways critical to learning and memory 1. Loss-of-function variants cause intellectual developmental disorder with behavioral abnormalities and craniofacial dysmorphism with or without seizures (IDDBCS), characterized by neurodevelopmental delay, overgrowth, craniofacial anomalies, and frequently developmental and epileptic encephalopathy 56. Zebrafish models confirm that PHF21A deficiency impairs brain morphogenesis and causes epileptiform discharges 7. De novo frameshift and nonsense variants represent the primary pathogenic mechanisms in this neurodevelopmental disorder.