Tjp2, also known as ZO-2, encodes a tight junction protein. Liver tight junctions established by Tjp2 isolate bile from the blood circulation. Tjp2 is involved in maintaining the normal cortical distribution of radixin, canalicular volume regulation, and microvilli density in the liver [1].

In mice with liver-specific inactivation of Tjp2 (Tjp2 cKO mice), there are lower Cldn1 protein levels, minor TJ changes, dilated canaliculi, lower microvilli density, and abnormal radixin and BSEP distribution. These mice present with mild progressive cholestasis, lower expression of bile acid transporter Abcb11/Bsep and detoxification enzyme Cyp2b10. They are more susceptible to cholic acid-induced liver injury. Hepatocyte-specific Tjp2 inactivation can lead to hepatocyte to cholangiocyte transdifferentiation in response to a DDC-supplemented diet, which requires Yap and Wwtr1/Taz whose protein expression is upregulated in hepatocytes lacking Tjp2 [1,2].

In conclusion, Tjp2 is essential for maintaining normal liver structure and function related to bile acid transport and the integrity of tight junctions. Tjp2 cKO mouse models have revealed its role in cholestatic liver diseases, such as its involvement in the pathophysiology of progressive cholestasis and the transdifferentiation process in the liver [1,2].