PCDH17 (protocadherin 17) is a non-clustered protocadherin belonging to the δ2 subgroup, classified as a calcium-dependent cell-adhesion protein with diverse roles in neuronal and tumor biology 1. Primary Function: PCDH17 functions as a postsynaptic cell-adhesion molecule that restricts dendritic spine morphogenesis through ROCK2-dependent actin cytoskeleton regulation 2. Mechanism: PCDH17 binds ROCK2 to enhance downstream signaling through LIMK1 and cofilin phosphorylation, regulating F-actin organization and spine development 2. In vascular endothelium, PCDH17 interacts with E3 ubiquitin ligase MARCH5 to prevent VEGFR2 degradation, increasing vascular permeability 3. Disease Relevance: PCDH17 expression is frequently silenced in multiple cancers—including acute leukemia, gastric cancer, laryngeal carcinoma, ovarian cancer, and hepatocellular carcinoma—primarily through promoter hypermethylation mediated by histone deacetylation and DNMT3B activity 45678. PCDH17 downregulation promotes cancer cell proliferation, migration, invasion, and metastasis through epithelial-mesenchymal transition 83. Clinical Significance: PCDH17 is implicated in neuropsychiatric disorders including bipolar disorder and depression 2, and serves as a tumor suppressor candidate with prognostic value across multiple malignancies.