Plakophilin 4 (PKP4)

Plakophilin 4 (PKP4), also known as p0071, is a member of the armadillo-repeat protein family and the p120-catenin subfamily, primarily functioning as a scaffold protein at adherens junctions and desmosomes (Hatzfeld et al., 1996; 2003). It plays a critical role in maintaining cell-cell adhesion, regulating cytoskeletal organization through Rho GTPase signaling (specifically RhoA and Ect2), and modulating the Hippo pathway to influence cell proliferation (Müller and Hatzfeld, 2025). In oncology, PKP4 is frequently overexpressed in various malignancies, including non-small cell lung cancer and breast cancer, where it promotes epithelial-mesenchymal transition (EMT), invasion, and metastasis (Medvetz et al., 2012). A unique aspect of PKP4 as a therapeutic target is the spatial regulation of its mRNA; PKP4 mRNA localizes to the protrusions of migrating metastatic cells, a process that facilitates local protein synthesis and directional movement (Mili et al., 2008). Therapeutic interventions targeting PKP4 mRNA, such as siRNAs or miRNA mimics like miR-1298, aim to downregulate its expression or disrupt its localization to inhibit tumor progression (Gao et al., 2021). Additionally, PKP4 mRNA is a known target of the Fragile X Mental Retardation Protein (FMRP), suggesting potential roles in neurodevelopmental disorders (NIH, 2025).

Other names

p0071Plakophilin-4PKP4 mRNA

Inhibition of translation, degradation of mRNA, or interference with mRNA localization via RNA interference (siRNA/shRNA) or miRNA-mediated silencing.