In CRC, it promotes tumor invasiveness by controlling the crypt-villous expression gradient and epithelial homeostasis.[21,22] In SLE-like autoimmune settings, EPHB2 drives immune cell activation and fibrosis, as evidenced in systemic sclerosis where it enhances extracellular matrix deposition and inflammation.[23] This implies that SLE’s chronic inflammatory state could upregulate EPHB2, bridging to CRC by enabling immune-mediated epithelial disruption and metastasis. This evidence concerns the gene EPHB2 and neoplasm.