PKP2, or plakophilin-2, is a component of the desmosome complex crucial for cell-cell adhesion [3]. It has been associated with multiple biological pathways and is of great biological importance, especially in cardiac function and cancer development. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In arrhythmogenic cardiomyopathy, AAV-mediated delivery of PKP2 in PKP2 mutant induced pluripotent stem cell-derived cardiomyocytes restored PKP2 and other junctional protein levels, improved sodium conduction, enhanced contractile function, and normalized contraction kinetics. Treating heterozygous Pkp2 knock-in mice in vivo also corroborated the recovery of desmosomal integrity and cardiac function [2]. In gastric cancer, PKP2 was upregulated, and the YAP1/TEAD4 complex could stimulate its transcriptional expression. Elevated PKP2 levels facilitated activation of the AKT/mammalian target of rapamycin signaling pathway, promoting the malignant progression of gastric cancer, which was validated in a mouse model [1].

In conclusion, PKP2 plays essential roles in cell-cell adhesion, cardiac function, and cancer progression. The use of KO/CKO mouse models has been instrumental in revealing its role in arrhythmogenic cardiomyopathy and gastric cancer, providing insights into potential therapeutic targets for these diseases.