PCDH20 is a non-clustered δ1-protocadherin functioning as a calcium-dependent cell adhesion molecule with critical roles in epithelial homeostasis and tumor suppression 1. In the intestinal epithelium, PCDH20 maintains barrier integrity by stabilizing adherens junctions through β-catenin and p120-catenin regulation via the ATF6/CHOP signaling axis 2. PCDH20 is downregulated in Crohn's disease patients, and its loss causes enterocyte dysfunction and exacerbates colitis in mouse models 2. PCDH20 functions as a tumor suppressor across multiple cancer types through antagonizing Wnt/β-catenin signaling and suppressing epithelial-mesenchymal transition, with frequent epigenetic inactivation via promoter methylation observed in nasopharyngeal and hepatocellular carcinomas 34. In hepatocellular carcinoma, PCDH20 promotes ferroptosis by suppressing SIRT1 and promoting NRF2 acetylation, reducing ferroptosis-protective factors like GPX4 and GSH 5. Additionally, PCDH20 is implicated in auditory function, with genetic variants associated with hearing thresholds, likely through regulatory sequence variation affecting expression in inner ear hair cells 6. In the olfactory system, PCDH20 shows sexually dimorphic expression in sensory neurons during development, suggesting roles in neural circuit formation 7.