CSNK2B encodes the regulatory beta subunit of casein kinase 2 (CK2), a serine/threonine protein kinase complex essential for multiple cellular processes. The protein functions as a key regulator of CK2 holoenzyme formation and stability, where pathogenic variants in the zinc-finger domain significantly reduce protein stability and homodimerization capacity 1. CSNK2B plays critical roles in cellular signaling pathways, including negative regulation of autophagy through interaction with TRIM family proteins, where it phosphorylates TRIM3 at serine 661 to inhibit autophagosome formation 2. The protein also modulates antiviral responses by enhancing IRF1 binding to chr6 and promoting transcription of antiviral genes like PLAAT4, while simultaneously regulating AFAP1-Src signaling 3. Additionally, CSNK2B activates ATF6-mediated ER stress responses in intestinal epithelial cells, contributing to inflammatory signaling in conditions like Crohn's disease 4. Disease relevance includes Poirier-Bienvenu neurodevelopmental syndrome, where de novo variants cause intellectual disability, developmental delay, and epilepsy with broad phenotypic severity ranging from treatable seizures to intractable epilepsy 5. The protein is also implicated in various cancers, including adult T cell leukemia/lymphoma and clear cell renal cell carcinoma 67.