CLDN1 and TJP2 encode integral TJ proteins; mutations in CLDN1 were found in neonatal ichthyosis-sclerosing cholangitis syndrome (NISCH) and TJP2 mutations cause familial hypercholanemia (FHC) and a newly described subtype of Progressive Familial Intrahepatic Cholestasis syndrome (PFIC-4) [50,51,91]. Here, TJP2 is linked to hypercholanemia, familial.