It has been hypothesized that the lack of response to UDCA in some PBC patients may indicate a failure to upregulate alk-SMase, another nucleotide pyrophosphatase/phosphodiesterase (NPP) enzyme similar to autotaxin, by UDCA in these patients, leading to increased levels of autotaxin35. The gene discussed is ENPP2; the disease is primary biliary cholangitis.