AKIP1 (A-kinase interacting protein 1) is a nuclear protein that enhances NF-κB transcriptional activity through multiple mechanisms. Its primary function involves promoting nuclear localization and phosphorylation of the NF-κB p65 subunit by facilitating protein kinase A (PKA) interaction with p65 at serine-276 1. AKIP1 acts as a scaffold protein that coordinates PKA-mediated p65 phosphorylation, nuclear retention, and enhanced NF-κB-dependent gene expression 1. Clinically, AKIP1 is markedly overexpressed across multiple cancer types including esophageal squamous cell carcinoma, breast, prostate, cervical, and glioblastoma cancers 234. Meta-analysis of 3,979 cancer patients demonstrates that high AKIP1 expression significantly predicts poor overall survival (HR=1.86) and disease-free survival (HR=1.69), and correlates with adverse clinicopathological features including advanced tumor stage, lymph node metastasis, and treatment resistance 56. Mechanistically, AKIP1 promotes cancer progression through multiple pathways: it upregulates VEGF-C to drive angiogenesis and lymphangiogenesis 2, activates EMT via the PI3K/Akt/IKKβ pathway 3, stabilizes EGFR through HSP90α cooperation 4, and is regulated by deubiquitination via the UBE2S/USP15 axis 7. AKIP1 represents a promising therapeutic target and biomarker for cancer prognosis.