Phosphorylation of NF-κB p65 at Ser529 is a post-translational modification that plays a significant role in the regulation of NF-κB activity. This modification is catalyzed by casein kinase II (CK2) upon stimulation by cytokines such as interleukin-1β (IL-1β) or tumor necrosis factor α (TNFα), leading to increased p65 transactivation potential in a gene-specific manner. Phosphorylation at S529 enhances the transcriptional activity of NF-κB, which is crucial for regulating various cellular processes including inflammation, immune responses, and cell survival. Dysregulation of NF-κB signaling, including phosphorylation at S529, has been implicated in various diseases, particularly in the context of chronic inflammation and aging. Phosphorylation of p65 at S529 has also been reported to promote tumorigenesis in various tissues, including the bone, breast, and head and neck, suggesting a significant role of NF-κB phosphorylation in different types of cancers.