Rbl1, also known as p107, is a member of the retinoblastoma (RB) protein family, which are critical modulators of the cell cycle. Dysregulation of Rbl1 has been associated with tumor initiation and progression. Its activity is regulated by multiple pathways, including those directly or indirectly linked to Ca2+-dependent signaling [1].

In Xenopus tropicalis, combined inactivation of rb1 and rbl1 is required to drive small-cell pancreatic neuroendocrine carcinoma (SC-PaNEC), retinoblastoma, and astrocytoma, suggesting Rbl1 functions as a tumor suppressor [3]. In mouse models, loss of Rb1/Rbl1/Vhl generates subretinal vascular growths resembling retinal angiomatous proliferation (RAP) and retinal capillary hemangioblastoma (RCH), indicating the Rb family limits Hif target gene expression in the Vhl -/- retina [2]. In human embryonic stem cells, depletion of RBL1 along with RB and RBL2 impairs subsequent differentiation into foregut endoderm, suggesting RB proteins are essential for generating advanced derivatives after primary germ layer formation [4].

In conclusion, Rbl1 is a key regulator in the cell cycle and plays a significant role as a tumor suppressor in various cancer types, as demonstrated by in vivo studies in model organisms. It also contributes to the proper differentiation of embryonic stem cells. The study of Rbl1 using gene knockout models has provided valuable insights into its functions in cancer development and early embryonic development.