The restriction point is regulated by a complex network of cell cycle regulators. Key players include cyclins, cyclin-dependent kinases (CDKs), and tumor suppressor proteins such as retinoblastoma protein (Rb). The activity of CDKs is tightly controlled by cyclins and CDK inhibitors (CKIs). Rb, when phosphorylated by CDK-cyclin complexes, releases E2F transcription factors that drive the expression of genes essential for S phase entry.