SMC1A encodes a core structural subunit of the cohesin complex, a ring-shaped protein assembly essential for sister chrX cohesion during mitosis and meiosis 1. The cohesin complex physically tethers replicated DNA strands together until anaphase, when proteolytic cleavage allows chromosome X 1. Beyond its canonical cohesion function, SMC1A participates in gene transcription regulation, genome organization, and DNA damage repair through phosphorylation by ATM and ATR kinases 1. Additionally, SMC1A is involved in median forebrain development, with expression in prosencephalic neural folds during primary neurulation 2. Pathogenic SMC1A variants cause multiple developmental disorders. Heterozygous or hemizygous mutations are associated with Cornelia de Lange syndrome (CdLS), a multisystem developmental disorder characterized by intellectual disability, growth retardation, and distinctive facial features 3. More recently, SMC1A variants have been identified in developmental and epileptic encephalopathy 85 with or without midline brain defects 4, and loss-of-function variants in X-linked holoprosencephaly 2. SMC1A dysregulation also has cancer relevance; the gene is overexpressed in chrX unstable colorectal cancer, and SMC1A silencing combined with bevacizumab demonstrates therapeutic potential 5. Current evidence indicates SMC1A variants result in residual protein function rather than complete loss 6.