WDR46 is a scaffold protein essential for ribosomal small subunit (SSU) biogenesis in the nucleolus. As a component of the SSU processome—the initial precursor of eukaryotic ribosomal small subunits—WDR46 functions as a structural organizer of pre-rRNA processing machinery 1. The protein exhibits low mobility within nucleoli and binds tightly to macro-protein complexes, acting as a core scaffold component 2. Mechanistically, WDR46 determines the granular compartmental localization of nucleolin and DDX21, factors involved in 18S rRNA processing, through interactions mediated by its intrinsically disordered terminal regions 1. Disease relevance includes HBV-associated hepatocellular carcinoma, where HBC protein stabilizes WDR46 by reducing TRIM25-mediated ubiquitination, leading to NUSAP1 upregulation and enhanced HCC cell proliferation and migration 3. WDR46 is also implicated in gastrointestinal disease risk through pollution-related alterations in DNA methylation and gene expression 4, and was identified as a core gene in acquired immunodeficiency with complications 5. Additionally, WDR46 genetic variants associate with aspirin-exacerbated respiratory disease risk and FEV1 decline in Korean populations 6. In Adriamycin-resistant lymphoma, WDR46 downregulation contributes to paclitaxel's therapeutic effects through ribosome biosynthesis pathway modulation 7.