Whereas Hani et al. [8] identified HNF4A mutations as being causative in maturity-onset diabetes of the young (MODY type 1, OMIM #125850) based on a nonsense mutation (p.Q268X) in an extended pedigree, many other seemingly functional variants have turned out to be either innocent bystanders or of relatively low penetrance. This evidence concerns the gene HNF4A and type 2 diabetes mellitus.