Rbl1, also known as p107, is a member of the retinoblastoma (RB) protein family. Along with RB1/p105 and RBL2/p130, it is a critical modulator of the cell cycle. Rbl1's activity is regulated by multiple signaling pathways, with its expression levels being modulated by pathways related to Ca2+-dependent signaling, such as those involving multifunctional calcium/calmodulin-dependent kinases (CaMKs) and the Ca2+-dependent endopeptidase calpain [1]. It is also associated with tumor suppression, as alterations in the retinoblastoma signaling network, including Rbl1, are linked to specific cancers [3].

In Xenopus tropicalis, combined inactivation of rb1 and rbl1 by multiplex Nuclease technology genome editing was required and sufficient to drive small-cell pancreatic neuroendocrine carcinoma (SC-PaNEC), retinoblastoma, and astrocytoma, indicating Rbl1 functions as a tumor suppressor in these contexts [3]. In mice, Rb1/Rbl1/Vhl loss induced subretinal angiomatous proliferation and hemangioblastoma, suggesting that the Rb family, including Rbl1, limits Hif target gene expression in the Vhl -/- retina [2].

In conclusion, Rbl1 is a key cell cycle regulator and tumor suppressor. The use of gene-editing techniques in animal models, like in Xenopus tropicalis and mice, has been crucial in revealing its role in tumorigenesis and specific disease-related processes such as subretinal vascular growths. These findings enhance our understanding of the biological functions of Rbl1 and its implications in diseases related to cell cycle dysregulation and tumor development.