CLMP (CXADR-like membrane protein) is an immunoglobulin superfamily cell adhesion molecule that functions as a tight junction-associated protein 1. Structurally related to the coxsackie-adenovirus receptor (CAR), CLMP mediates homotypic cell aggregation and is composed of one V-set and one C2-set immunoglobulin domain 2. CLMP plays critical roles in intestinal development and homeostasis. Loss-of-function CLMP mutations cause congenital short bowel syndrome (CSBS), characterized by defective intestinal elongation during embryogenesis and impaired peristalsis driven by uncoordinated calcium signaling in smooth muscle via reduced connexin43 and connexin45 levels 34. In the colonic epithelium, CLMP suppresses cell proliferation through mTOR-Akt-β-catenin signaling pathways 5. CLMP functions as a colorectal cancer tumor suppressor by recruiting β-catenin to the cell membrane, independent of cadherin proteins, thereby inactivating oncogenic Wnt/β-catenin signaling 1. CLMP deficiency increases CRC tumorigenesis and promotes resistance to all-trans retinoic acid (ATRA) therapy by upregulating CYP26A1, which metabolizes ATRA 1. These findings suggest CYP26A1 inhibitors could enhance ATRA therapeutic efficacy in CLMP-deficient colorectal cancers.