Rbbp6, or Retinoblastoma binding protein 6, is a cancer-related protein with an E3 ubiquitin ligase function. It is involved in multiple cellular processes such as cell cycle regulation, apoptosis, and pre-mRNA 3' end processing. It interacts with tumor suppressors like p53 and pRB, and its isoforms have different domain compositions, which may contribute to its diverse functions [2].

In glioblastoma, Nuclease technology knockout screens revealed RBBP6 as essential for glioblastoma stem cell (GSC) maintenance. Targeting RBBP6 inhibited GSC proliferation and tumor initiation. Mechanistically, it mediates K63-linked ubiquitination of CPSF3 to regulate alternative polyadenylation, influencing MYC expression [1].

In renal tubular cells of diabetic kidney disease models, RBBP6 promotes the degradation of ERRα through K48-linked polyubiquitination, contributing to mitochondrial injury. Conditional ERRα overexpression or RBBP6 inhibition reduced mitochondrial damage [3].

In ovarian cancer, knockdown of RBBP6 attenuated cell proliferation and migration, and in nude mice, it slowed tumor growth [4].

In colorectal cancer, RBBP6 promoted cell proliferation, migration, invasion, and metastasis in cell and mouse models by ubiquitinating and degrading IκBα to activate the NF-κB pathway [5].

In conclusion, Rbbp6 is a multifunctional protein involved in cell cycle, apoptosis, and mRNA processing. Gene knockout-based research in models has shown its significant roles in diseases like glioblastoma, diabetic kidney disease, ovarian cancer, and colorectal cancer. Understanding Rbbp6 functions provides potential therapeutic targets for these diseases.