Recently, a nonsense mutation (c.376C>T) of LGR4, which abolishes the signal transduction of LGR4, has been reported in humans to be strongly associated with low bone mineral density, osteoporotic features, electrolyte imbalances, reduced testosterone levels, and increased risk of cutaneous squamous cell cancers and biliary tract cancers [28]. This evidence concerns the gene LGR4 and biliary tract cancer.