The article reports the cloning and characterization of p57KIP2, a new member of the CDK inhibitor (CDI) family. p57KIP2 is distinguished from other CDIs like p21CIP1 and p27KIP1 by its unique domain structure and tissue-specific expression pattern. The protein contains four distinct domains: a CDK inhibitory domain, a proline-rich domain, an acidic domain, and a nuclear targeting domain. p57KIP2 is a potent inhibitor of G1 and S-phase CDKs, including cyclin E-cdk2, cyclin D2-cdk4, and cyclin A-cdk2, but to a lesser extent of the mitotic cyclin B-Cdc2. In mammalian cells, p57KIP2 localizes to the nucleus and overexpression causes a complete cell cycle arrest in the G1 phase. The expression of p57KIP2 is tissue-specific, with higher levels in placenta and lower levels in other tissues. The unique domain structure and restricted tissue distribution suggest that p57KIP2 may play a specialized role in cell cycle control.The article reports the cloning and characterization of p57KIP2, a new member of the CDK inhibitor (CDI) family. p57KIP2 is distinguished from other CDIs like p21CIP1 and p27KIP1 by its unique domain structure and tissue-specific expression pattern. The protein contains four distinct domains: a CDK inhibitory domain, a proline-rich domain, an acidic domain, and a nuclear targeting domain. p57KIP2 is a potent inhibitor of G1 and S-phase CDKs, including cyclin E-cdk2, cyclin D2-cdk4, and cyclin A-cdk2, but to a lesser extent of the mitotic cyclin B-Cdc2. In mammalian cells, p57KIP2 localizes to the nucleus and overexpression causes a complete cell cycle arrest in the G1 phase. The expression of p57KIP2 is tissue-specific, with higher levels in placenta and lower levels in other tissues. The unique domain structure and restricted tissue distribution suggest that p57KIP2 may play a specialized role in cell cycle control.