The normal progression of cells through the cell cycle is under the control of the cyclin dependent protein kinases Cdk4 and Cdk6 which are subject to inhibition by the mitotic inhibitory protein p16. Isolated members of the p16 family have been designated p15 and p18, respectively. The p16 related protein, p18, interacts strongly with Cdk6 and to a lesser extent with Cdk4, but lacks apparent interaction with other Cdks. Recombinant p18 has been shown to inhibit cyclin D-Cdk6 kinase activity. In contrast to p21/p27 that form ternary complexes with cyclin-Cdks, only binary complexes of p15, p16 and p18 have been identified in association with Cdk4 and/or Cdk6.