A whole-exome sequencing reported the somatin mutations of RNF43, targeting the frizzled receptor for its ubiquitination and degradation to block WNT signaling activation, in 14% (8/57) of frozen intraductal papillary mucinous neoplasms of the pancreas.78 In addition, they first revealed the significant association between RNF43 mutation in frozen samples and downregulated RNF43 expression in 52 (29.5%) of the 176 surgically resected cases, suggesting the reduced expression of RNF43 may result from its mutations. This evidence concerns the gene RNF43 and pancreatic intraductal papillary-mucinous neoplasm.