Our co-IP data indicate that ZNRF3/RNF43 interact with EGFR through their extracellular domains It would also be interesting to determine further the specific domains and amino acids that are responsible for ZNRF3/RNF43 and EGFR interaction and to study whether clinically relevant point mutations at the extracellular domains of ZNRF3/RNF43 and/or EGFR hinder their binding affinity, thereby enhancing EGFR signaling to promote cancer initiation and progression. The gene discussed is ZNRF3; the disease is cancer.