A cyclin-dependent kinase inhibitor protein (also known as CKIs, CDIs, or CDKIs) is a protein which inhibits the enzyme cyclin-dependent kinase (CDK) and Cyclin activity by stopping the cell cycle if there are unfavorable conditions, therefore, acting as tumor suppressors. Cell cycle progression is stopped by Cyclin-dependent kinase inhibitor protein at the G1 phase.^[2] CKIs are vital proteins within the control system that point out whether the process of DNA synthesis, mitosis, and cytokines control one another. If a malfunction prevents the successful completion of DNA synthesis during the G1 phase, a signal is sent to delay or stop the progression to the S phase. Cyclin-dependent kinase inhibitor proteins are essential in the regulation of the cell cycle. If cell mutations surpass the cell cycle checkpoints during cell cycle regulation, it can result in various types of cancer.^[3]

Cyclin-dependent kinase inhibitor proteins work by inactivating the CDKs by degradation. The typical inactivation mechanism of the CDK/ Cyclin complex is based on binding a CDK inhibitor to the CDK cyclin complex and a partial conformational rotation of the CDK.^[4] The cyclin is thus forced to release the T loop and detach from the CDK. Then, the CDK inhibitor initiates a small Helix into the cleft blocking the cleft and blocking the active site of the CDK. Eventually, it releases the ATP out of the aperture of the CDK and deactivates it. Cyclin-dependent kinase inhibitor proteins use ATP as a phosphate contributor to phosphorylate serine and threonine residues.^[5][6]  

Human cells contain many different cyclins binding to different CDKs. CDKs and cyclins appear and activate at specific cell cycle phases. Seven cyclin-dependent kinase inhibitor proteins have been identified. They are p15, p16, p18, p19, p21, p27, and p57.^[7] These cyclin-dependent kinase inhibitor protein emerges only in their specific cell cycle phase.^[7] Each Cyclin/CDK complex are specific to the part of the cell cycle phase. Each CDK and cyclin can be identified based on the location of the cell cycle. CKIs fall within two categories; those that inhibit CDKI, CDK2, and CDK5 and those that inhibit CDK4 and CDK6. These checkpoints' cell cycle blocks at both the G1/S and G2/M checkpoints are consistent with the inhibition profile of the enzymes.

In the cyclin-dependent kinase (CDK) family or CDK, Cyclin, and CKIs, serine/threonine kinases play an integral role in regulating the eukaryotic cell cycle. The structure of CDK2-CyclinA and p27 is determined by crystallography, demonstrating that the inhibitor of p27 stretches at the top of the Cyclin-CDK complex. The amino terminal of p27 has an RXL motif exhibiting a hydrophobic patch of cyclin A. The carboxyl-terminal end of the p27 fragment interacts with the beta sheet of CDKs, causing interference of the structure; p27 slides into the ATP- binding site of CDK2 and inhibits ATP binding.^[5]