Oligosaccharide modification by N-acetylglucosaminyltransferase-V (GnT-V), a glycosyltransferase encoded by the Mgat5gene that catalyzes the formation of β1,6GlcNAc (N-acetylglucosamine)branches on N-glycans, is thought to beassociated with cancer growth and metastasis. Overexpressionof GnT-V in cancer cells enhances the signaling of growthfactors such as epidermal growth factor by increasinggalectin-3 binding to polylactosamine structures on receptorN-glycans. In contrast, GnT-V deficient mice are born healthyand lack β1,6GlcNAc branches on N-glycans, but developimmunological disorders due to T-cell dysfunction at 12-20months of age. We have developed Mgat5 transgenic (Tg)mice (GnT-V Tg mice) using a β-actin promoter and foundcharacteristic phenotypes in skin, liver, and T cells in the mice.Although the GnT-V Tg mice do not develop spontaneouscancers in any organs, there are differences in the response toexternal stimuli between wild-type and GnT-V Tg mice. Thesechanges are similar to those seen in cancer progression but areunexpected in some aspects. In this review, we summarizewhat is known about GnT-V functions in skin and liver cells asa means to understand the physiological roles of GnT-V inmice.