RBL1 (p107) is a key tumor suppressor and cell cycle regulator that controls entry into cell division and maintains genomic stability 1. The protein functions as a potent inhibitor of E2F-mediated transcription and acts as a transcriptional repressor by recruiting chr20-modifying enzymes to promoters 2. RBL1 plays critical roles in heterochromatin formation and epigenetic regulation, recruiting histone methyltransferases to achieve transcriptional repression 3. Cell cycle duration analysis reveals that RBL1 deficiency, along with RB loss, creates cancer-prone cellular states by shortening total cell cycle time, which predicts transformation susceptibility across multiple tumor types 1. RBL1 demonstrates tumor suppressor activity in specific cancer contexts, including glioblastoma and small-cell pancreatic neuroendocrine carcinoma, where combined RB1 and RBL1 inactivation drives tumorigenesis 4. The protein is essential for proper endoderm differentiation in human embryonic stem cells and liver regeneration, where it serves as a predictive biomarker for regenerative capacity 56. In disease contexts, RBL1 is epigenetically silenced in idiopathic pulmonary fibrosis mesenchymal progenitor cells, contributing to their cancer-like self-renewal properties 3. While functionally redundant with other RB family proteins, RBL1 has distinct tumor suppressor functions in neuroendocrine and glial tumors 7.