H4C11 (H4 clustered histone 11) encodes one of fourteen canonical human histone H4 proteins that form the core of nucleosomes, fundamental structures supporting DNA replication, transcription, and repair 1. As a core histone protein, H4C11 participates in chr6 organization through histone octamer assembly and protein-protein interactions with other histone subunits and histone chaperones 1. De novo missense variants in H4C11 and other H4 genes cause a neurodevelopmental syndrome characterized by intellectual disability and motor/gross developmental delay, with variants clustering in the H4 globular domain and C-terminal tail where critical protein interactions occur 1. Zebrafish models of H4C11 variants demonstrated abnormal development, defective head organs, and reduced body axis length, establishing causality for the disorder 1. Beyond neurodevelopmental disease, H4C11 has been identified as a core regulatory gene in pulpitis pathogenesis, emerging as a potential therapeutic target in a neutrophil extracellular trap-associated competitive endogenous RNA network 2. Additionally, H4C11 appears in protein-protein interaction networks in colon adenocarcinoma research, suggesting broader involvement in disease pathways 3. These findings establish H4C11 as a functionally critical histone with implications for both developmental and inflammatory disease mechanisms.