PDLIM2 (PDZ and LIM domain 2) is a cytoskeletal adapter protein that functions as a critical regulator of transcription factor stability and cellular signaling pathways. The protein primarily operates by promoting the degradation of key transcription factors including NF-κB/RelA, STAT3, and β-catenin through E3 ligase-mediated ubiquitination mechanisms 1. PDLIM2 bridges STAT3 with E3 ligases PDLIM2 and PDLIM5, facilitating STAT3 degradation 2, and can interact with circular RNAs like circPTPN12 to enhance P65 ubiquitination 3. The protein exhibits complex, context-dependent roles in cancer, functioning as a tumor suppressor when its expression is epigenetically silenced through promoter hypermethylation in lung, breast, and ovarian cancers 1. In contrast, PDLIM2 can promote oncogenic phenotypes in certain contexts, particularly in castration-resistant prostate cancer where its suppression reduces tumor growth, proliferation, and invasiveness through MAPK/ERK pathway modulation 4. PDLIM2 downregulation in lung cancer leads to mitochondrial dysfunction, oncometabolite accumulation, and HIF-1α activation, contributing to tumor progression 5. The protein also plays important roles in immune regulation, particularly in controlling regulatory T cell function and tumor immunity 12.