The finding that RIZ2 overexpression enhances the EGF/EGFR pathway strongly suggests a not-negligible role of PRDM2 isoforms in the control of several oncogenic networks involved in CRC encompassing oncogenic pathway crosstalk, tumor microenvironment remodeling, tumor immune-escape, plasticity and stemness. The gene discussed is PRDM2; the disease is colorectal carcinoma.