CTCF and Intellectual disability: Building on the observation that a clinically heterozygous CTCF mutation at c.1699 C > T (p.Arg567 > Trp) induces severe phenotypes, including intellectual disability, microcephaly, hypotonia, growth deficiency, delayed development, short stature, delayed bone age, and feeding difficulties17,19,20,26,27, we establish a Ctcf mutant mouse model and a human embryonic stem cell (hESC)-derived cortical organoid model harboring the CTCFR567W mutation to explore its mechanistic involvement.