RBBP6 (retinoblastoma binding protein 6) is a multifunctional E3 ubiquitin ligase that plays critical roles in mRNA processing, cell cycle regulation, and cancer progression. The protein functions as an essential component of the pre-mRNA 3' end processing machinery, where it anchors this process to nuclear speckles through its C-terminal intrinsically disordered region, facilitating efficient gene expression 1. RBBP6 contains a unique ubiquitin-like DWNN domain that mediates interactions with core polyadenylation factors and is required for 3' processing activity 2. The gene produces multiple isoforms, including a smaller isoform 3 (iso3) that competitively inhibits 3' processing by blocking RBBP6's interaction with the core machinery 2. RBBP6's ubiquitin ligase activity targets several key proteins: it promotes p53 degradation in lung cancer cells, thereby enhancing proliferation and inhibiting apoptosis 3, and it mediates K48-linked ubiquitination of ERRα, contributing to mitochondrial dysfunction in diabetic kidney disease 4. In glioblastoma, RBBP6 maintains stem cell properties through K63-linked ubiquitination of CPSF3, regulating alternative polyadenylation events that affect MYC expression 5. RBBP6 is overexpressed in multiple cancers and represents a potential therapeutic target 67.