BAs and activation of their downstream targets including G-protein-coupled bile acid receptor (TGR5), transforming growth factor-α (TGF-α) and sphingosine-1-phosphate receptor-2 (S1PR2) stimulate cholangiocyte proliferation and contribute to the progression of cholangiocarcinoma [CCA, in vivo and in vitro (21–25)]. The gene discussed is S1PR2; the disease is cholangiocarcinoma.