CDH4 encodes R-cadherin, a calcium-dependent cell adhesion protein that primarily functions in homophilic cell-cell adhesion and tissue organization 1. The protein plays critical roles in normal development, particularly in ocular development where it is expressed in the optic fissure and periocular mesenchyme, with knockdown leading to coloboma phenotypes 2. CDH4 also contributes to neurological function, with elevated expression in multiple system atrophy brain tissue affecting α-synuclein levels in oligodendrocytes 3. In cancer contexts, CDH4 demonstrates complex roles: it acts as a tumor suppressor in gastrointestinal cancers through promoter methylation-mediated silencing 1, but functions oncogenically in osteosarcoma by promoting migration, invasion, and stemness through JNK/c-Jun pathway activation 4. In oral squamous cell carcinoma, CDH4 promotes proliferation and inhibits ferroptosis, correlating with poor patient survival 5. The gene also shows protective associations against bronchopulmonary dysplasia 6 and contains polymorphic Alu elements that contribute to human longevity 7. Additionally, CDH4 harbors a novel microRNA (hsa-miR-B43) with potential metastasis-related functions in breast cancer 8.