Phospho-NF-κB p65 (Ser536) refers to the phosphorylation of the p65 subunit of the NF-κB protein complex at the serine 536 residue. This post-translational modification is crucial for regulating the transcriptional activity, nuclear localization, and protein stability of NF-κB, which is a master regulator of inflammation and cell survival. Phosphorylation at Ser536 has been shown to negatively regulate NF-κB p65 activity. In a study published in Sci Signal, it was demonstrated that mice expressing a mutant p65 with an alanine-to-serine substitution at position 534 (the murine homolog of human Ser536) exhibited increased expression of NF-κB-dependent genes upon inflammatory stimulation, leading to enhanced inflammation and increased mortality. The phosphorylation status of NF-κB p65 at Ser536 is also associated with the prognosis of certain cancers. For instance, in colorectal cancer, increased expression of phospho-Ser536-p65 in the cytoplasm of primary tumors correlates with worse patient survival, independent of other clinical factors, making it an independent prognostic factor. Moreover, the phosphorylation of NF-κB p65 at Ser536 has been implicated in the pathogenesis of liver cancer.