CDH16 (cadherin 16) is a calcium-dependent cell adhesion protein primarily expressed in renal proximal tubular epithelial cells and thyroid tissue 12. As a homophilic cell adhesion molecule, CDH16 localizes to the basolateral plasma membrane where it facilitates cell-cell adhesion and contributes to maintaining epithelial cell differentiation and organization 2. CDH16 expression is developmentally regulated, appearing early in embryonic kidney and thyroid development and remaining dependent on TSH in differentiated thyrocytes 2. Clinically, CDH16 serves as a diagnostic marker for renal and thyroid malignancies. It is downregulated in papillary thyroid carcinomas (7% positive versus 100% in normal thyroid) and various renal cell carcinomas, with loss suggesting epithelial-mesenchymal transition 21. CDH16 demonstrates 85.3% sensitivity and 95.7% specificity for identifying renal tumors, improving to 96.8% specificity when combined with PAX8 3. CDH16 is also implicated in retinal dystrophy as a novel disease candidate 4 and serves as a kidney-specific promoter for gene editing studies in mouse models 56. Additionally, CDH16 expression in proximal tubular epithelial cells reflects their differentiation status, with loss correlating to lipotoxicity-induced dedifferentiation in metabolic kidney disease 7.