The mammalian CIP/KIP family proteins are intrinsically disordered proteins (IDPs) that can regulate various cellular processes. However, many reports have shown that IDPs generally evolve more rapidly than ordered proteins. Here, to elucidate the functional adaptability of CIP/KIP proteins in vertebrate, we analysed the rates of evolution in relation to their structural and sequence properties and predicted the post-translational modification based on the sequence data. The results showed that CIP/KIP proteins generally could maintain their function through evolution in the vertebrate. Basically, the disordered region that acts as a flexible linker or spacer has a conserved propensity for structural disorder and a persistent, fast rate of amino acid substitution, which could result in a significantly faster rate of evolution compared to the ordered proteins. Describing the pattern of structural order-disorder evolution, this study may give an insight into the well-known characteristics of IDPs in the evolution of CIP/KIP proteins.