As one of the selective adhesion molecule inhibitors, natalizumab binds to the α4 subunit of both α4β1 and α4β7 integrins, and antagonizes their interaction with all known ligands.17 It was approved in 2008 for the treatment of CD,23 but its large-scale use was limited because of PML.24,25 Over the past 7 years, >3000 patients have been exposed to vedolizumab, and no cases of PML have been observed.40 This can be explained by the relative gut selectivity of vedolizumab in antagonizing α4β7–MAdCAM-1 interactions.29–34. The gene discussed is MADCAM1; the disease is Cowden disease.