INCA1 is a novel cyclin-dependent kinase (CDK) inhibitor that functions as a negative regulator of cell cycle progression. It binds directly to cyclin A1-CDK2 complexes through a critical cyclin-binding domain, inhibiting CDK2 kinase activity 1. This binding interaction is essential for INCA1's function as a CDK inhibitor 1. INCA1 suppresses cell proliferation and regulates S-phase progression, serving as a co-factor for ING5-mediated growth suppression and apoptosis enhancement 2. In normal cells, mitogenic signals suppress INCA1 expression while cell cycle arrest induces it 1. Notably, INCA1 expression is significantly reduced in acute myeloid and lymphoid leukemia patients, highlighting its clinical relevance 1. INCA1(-/-) mice demonstrate increased CDK2 activity in spleen and elevated S-phase cell populations in fibroblasts 1. The protein can be negatively regulated through protein-protein interactions; the zinc finger protein HZF1 interacts with INCA1 and inhibits its function, thereby rescuing CDK2 activity 3. INCA1's expression is epigenetically regulated, with demethylation increasing expression in macrophages 4. This multifaceted regulation positions INCA1 as a critical growth suppressor frequently dysregulated in hematologic malignancies.