PKP4 (plakophilin 4) is an armadillo family protein that functions as a multifunctional scaffold at cell-cell junctions, coordinating adhesion with cytoskeletal organization and mechanical signaling. Primary function: PKP4 localizes at adherens junctions where it clusters cadherins and regulates cadherin recycling to enable junction dynamics 1. Mechanism: PKP4 controls spatio-temporal RhoA activity at junctions by scaffolding the Rho activator ARHGEF2 and effectors MLCK and MLC2, promoting cortical actin ring formation and tissue tension 2. It regulates small Rho-GTPases by controlling localization of guanine exchange factors (GEFs) and GTPase-activating proteins (GAPs) 1. Additionally, PKP4 directly interacts with KIF3B motor protein and cargo adaptor KAP3 to facilitate directional vesicle transport along microtubules 3. Disease relevance: PKP4 mutations have been identified in arrhythmogenic right ventricular cardiomyopathy patients, though their pathogenic significance requires further investigation 4. PKP4 is subject to miRNA-192 regulation in angiogenic processes 5. Clinical significance: In keratinocytes, PKP4 prevents differentiation while dampening proliferation through interaction with the Hippo pathway, controlling YAP/TAZ activity 1. PKP4 modulates Kir2.1-regulated inward rectifier potassium currents, suggesting roles in cardiac electrophysiology 6.