p21, also known as cyclin-dependent kinase inhibitor 1, is a cyclin-dependent kinase inhibitor that inhibits the complexes of CDK2 and CDK1. The p21 (CIP1/WAF1) protein binds to and inhibits the activity of cyclin-CDK2, -CDK1, and -CDK4/6 complexes, and thus functions as a regulator of cell cycle progression at G1 and S phase. In addition to growth arrest, p21 can mediate cellular senescence.

p21 mediates the resistance of hematopoietic cells to an infection with HIV[11] by complexing with the HIV integrase and thereby aborting chromosomal integration of the provirus. HIV infected individuals who naturally suppress viral replication have elevated levels of p21 and its associated mRNA. p21 expression affects at least two stages in the HIV life cycle inside CD4 T cells, significantly limiting production of new viruses. Metastatic canine mammary tumors display increased levels of p21 in the primary tumors but also in their metastases, despite increased cell proliferation.