PCDHA3 is a calcium-dependent cell adhesion protein predominantly expressed in the nervous system 1 that plays critical roles in neuronal connectivity and cell identity. As part of the clustered protocadherin-alpha family, PCDHA3 interacts with beta1-integrin to promote cell adhesion and forms oligomers with other protocadherin proteins at membrane sites 1. During neuronal maturation, PCDHA3 expression is dramatically downregulated by myelination 1. In cancer biology, PCDHA3 acts as a tumor suppressor; overexpression impairs lung squamous cell carcinoma proliferation, invasion, and migration by inhibiting epithelial-mesenchymal transition signatures 2. PCDHA3 has been implicated in neuropsychiatric disorders: maternal immune activation downregulates PCDHA3 in fetal mouse brains, linking genetic and environmental risk factors in schizophrenia pathogenesis 3. Ultra-rare missense mutations in PCDHA3 have been identified in schizophrenia cases, causing cytoplasmic aggregates and failure of homophilic plasma membrane interactions 4. Additionally, PCDHA3 variants segregate with familial restless legs syndrome 5 and have been associated with short root anomaly in Japanese populations 6, suggesting broader developmental roles beyond the nervous system.