TNFSF15 and Cowden disease: Since the discovery of the nucleotide oligomerization domain (NOD2) gene, numerous gene loci associated with abnormal innate immune responses (CARD15/NOD2, TLR4, CARD9, RAGE), differentiation of Th17-lymphocytes (IL-23R, JAK2, STAT3, CCR6, ICOSLG), autophagy (ATG16L1, IRGM, LRRK2, DEFB2/hBD2, SCL11A1), maintenance of epithelial barrier function (IBD5, DLG5, PTGER4, ITLN1, DMBT1, XBP1), and the initiation of secondary immune response (HLA-region, TNFSF15/TL1A, IRF5, PTPN2, PTPN22, NKX2-3, IL-12B, IL-18RAP, MST1) have been recognized for their role in CD pathogenesis (1, 2, 12–16).