PCDH11Y is a Y-linked protocadherin and calcium-dependent cell adhesion molecule 1 that is unique to humans and hominoids, arising from a gene duplication event approximately 6 million years ago 2. Primary functions include mediating cell adhesion and regulating excitatory neuron development in the central nervous system 3. The gene exists in three isoforms (11Ya, 11Yb, 11Yc) with distinct expression patterns 4. Mechanistically, PCDH11Y mediates Wnt signaling pathways critical for cell differentiation 4 and is upregulated by retinoic acid signaling during spermatogonial differentiation 4. Expression is predominantly localized to the cerebral cortex, hippocampal formation, and cerebellum during both fetal and adult development 2. The gene shows differential spatial distribution between X and Y homologs in the developing male CNS, suggesting specialized functions in male brain development 5. Disease relevance includes associations with male fertility, where PCDH11Yb expression in germ cells correlates with fertility status; absent or reduced expression is observed in infertile men 4. While initially implicated in psychiatric disorders and Alzheimer's disease susceptibility, subsequent studies found no significant associations with autism spectrum disorders, ADHD, bipolar disorder, obsessive-compulsive disorder, schizophrenia 1, or late-onset Alzheimer's disease 6. However, recent meta-analyses identified PCDH11Y as a potential AD biomarker with upregulated expression in patient populations 7.