This gene produces multiple transcript variants differing in their first exons. At least three variants encode distinct proteins; two yield related isoforms that inhibit CDK4 kinase, while a third uses an alternate exon 20 Kb upstream and encodes a structurally unrelated protein from an alternate reading frame (ARF). The ARF product stabilizes the tumor suppressor p53 by binding and sequestering MDM2, an E3 ligase that targets p53 for degradation. Despite structural differences, both CDK inhibitors and ARF regulate cell cycle G1 progression via CDK4 and p53 pathways. This gene is often mutated or deleted in many tumors and acts as a key tumor suppressor.