PCDH8 (protocadherin 8) is a calcium-dependent transmembrane cell-adhesion protein 1 belonging to the non-clustered δ2 protocadherin subfamily 2. It comprises three exons with an unusually compact genomic structure lacking introns in the extracellular domain 3. PCDH8 is predominantly expressed in the nervous system with region-specific patterns in the hippocampus and cortex 2, where it may facilitate activity-induced synaptic reorganization and dendritic spine regulation through CDH2 endocytosis via the TAOK2/p38 MAPK pathway 2. The protein signals through distinct intracellular partnerships, particularly with TAO2β 2. In disease contexts, PCDH8 functions as a candidate tumor suppressor across multiple cancer types. Low PCDH8 expression correlates with poor prognosis in ovarian cancer, and overexpression inhibits cell proliferation, invasion, and migration 4. Similarly, in esophageal squamous cell carcinoma, PCDH8 overexpression suppresses proliferation and angiogenesis via AKT pathway inhibition 5. In liver cancer, PCDH8 is frequently inactivated by promoter hypermethylation, associated with poor survival 6. However, in thyroid cancer, elevated PCDH8 correlates with poor prognosis and promotes proliferation 1, suggesting tissue-specific roles. Regarding neuropsychiatric disease, PCDH8 genetic variants show weak associations with schizophrenia susceptibility 7, though the precise contribution remains unclear.