Among genetic mechanisms, single-nucleotide variants (SNVs) or small insertions and deletions (indels) affecting the binding motifs or the structure of proteins implicated in establishing and/or maintaining the 3D genome structure—such as CTCF and cohesin—have the potential to rewire the 3D genome and gene expression, thus contributing to the cancer phenotype (Weisch et al., 2023). The gene discussed is CTCF; the disease is cancer.