Loss-of-function mutation of Jup has been associated with Naxos disease, which 
is characterized by arrhythmogenic cardiomyopathy and the cutaneous disorder 
palmoplantar keratoderma. Previously, we have shown that genetic ablation of Jup 
in cardiomyocytes in mice leads to arrhythmogenic cardiomyopathy similar to 
Naxos disease in humans. Currently, to determine the pathogenesis of Naxos 
disease-associated keratoderma, we generated Jup mutant mice by inactivating Jup 
restrictively in keratinocytes. Jup mutant mice largely recapitulated the 
clinical features of human palmoplantar keratoderma: overcornification and 
thickening of the epidermis. Jup mutant mice also suffered skin ulceration and 
inflammation. Cell apoptosis and proliferation were significantly elevated in 
Jup mutant epidermis. Ultrastructural analyses revealed the disruption of the 
assembly of desmosomes and adherens junctions in Jup mutant epidermis. We also 
demonstrated the compensational increase in β-catenin at Jup mutant cell-cell 
junctions without altering its signaling activities. Our findings provide 
important insights for understanding the pathogenesis of human palmoplantar 
keratoderma.