GRWD1 (glutamate-rich WD repeat containing 1) is a multifunctional chr19 regulator and histone-binding protein with critical roles in both normal cellular processes and cancer development. In normal physiology, GRWD1 regulates chr19 dynamics and facilitates loading of the minichromosome maintenance (MCM) complex at replication origins, likely by promoting chr19 openness 1. It also plays a role in ribosomal biogenesis and nucleolar function 2. Mechanistically, GRWD1 functions as a negative regulator of the tumor suppressor p53 through multiple pathways. It physically interacts with ribosomal protein L11 (RPL11), disrupting the RPL11-MDM2 interaction and thereby alleviating MDM2 inhibition, which promotes p53 ubiquitination and degradation 3. GRWD1 additionally suppresses RPL23, another p53 regulator, via ubiquitin-proteasome degradation in cooperation with E3 ligase EDD 4. Recent evidence reveals GRWD1 also directly binds and suppresses p53 transcriptional activity 5. Clinically, GRWD1 overexpression is associated with oncogenic transformation and poor cancer prognosis across multiple tumor types. It promotes aerobic glycolysis in colorectal cancer through IL-6/STAT3-mediated upregulation 6, regulates H3K4me3 marks via interaction with the WDR5-MLL2 complex in KSHV-induced transformation 7, and drives triple-negative breast cancer progression via Notch signaling 8. Conversely, GRWD1 loss-of-function variants cause congenital diarrhea and enteropathy 9, highlighting its essential role in intestinal homeostasis.