The mammalian cut proteins are a broadly expressed family of nuclear transcription factors related to the Drosophila protein cut. One member of the cut family, Cux1, has been shown to function as a cell cycle dependent transcription factor, regulating the expression of a number of cell cycle regulatory proteins. Cux1 expression is developmentally regulated in multiple tissues suggesting an important regulatory function. Cux1 exists as multiple isoforms that arise from proteolytic processing of a 200 kD protein or use of an alternate promoter. Several mouse models of Cux1 have been generated that suggest important roles for this gene in cell cycle regulation during hair growth, lung development and maturation, and genitourinary tract development. Moreover, the aberrant expression of Cux1 may contribute to diseases such as polycystic kidney disease and cancer. In this review, we will focus on the phenotypes observed in the five existing transgenic mouse models of Cux1, and discuss the role of Cux1 in kidney development and disease.