CDHR5 (cadherin related family member 5) is an intermicrovillar adhesion molecule essential for brush border organization in epithelial cells. CDHR5 forms calcium-dependent heterophilic complexes with CDHR2 on adjacent microvilli, controlling microvillar packing at the apical membrane 1. The protein is expressed as three dominant splice isoforms in intestinal epithelial cells, differing in a membrane-proximal extracellular mucin-like domain that restricts apical targeting through apparent hetero-oligomer formation 2. CDHR5 functions as part of the intermicrovillar adhesion complex (IMAC), which is critical for brush border differentiation and intestinal barrier function 3. Disease relevance includes tumor suppressor activity, as CDHR5 loss correlates with poor prognosis in colon cancer patients and its overexpression blocks tumor formation in colorectal cancer cell lines 4. However, CDHR5 shows context-dependent effects, promoting malignant phenotypes in pancreatic ductal adenocarcinoma 5. CDHR5 deficiency sensitizes to colitis and inflammatory bowel disease by compromising brush border structure and increasing bacterial invasion 3. The protein also shows altered methylation patterns in delayed cerebral ischemia following subarachnoid hemorrhage 6.