PNN (pinin, desmosome associated protein) is a multifunctional protein that serves dual roles in both nuclear RNA processing and cell adhesion. As a nuclear component, PNN functions as a transcriptional activator that binds to E-box sequences in the E-cadherin promoter and can reverse transcriptional repression 1. It serves as an auxiliary component of the exon junction complex (EJC) and participates in alternative pre-mRNA splicing regulation, associating with spliced mRNA within 60 nucleotides upstream of 5'-splice sites 1. In the cytoplasm, PNN maintains its original role as a desmosome-associated protein involved in establishing and maintaining epithelial cell-cell adhesion through connections with intermediate filaments 1. The protein demonstrates significant clinical relevance, functioning as a potential tumor suppressor for renal cell carcinoma and playing roles in cancer progression and metastasis 1. PNN expression levels correlate with various pathological conditions, including reduced expression associated with human dementia and protective roles against ischemic stress in astrocytes 1. In prostate cancer research, PNN has been identified as a hub gene related to bicalutamide resistance, highlighting its involvement in endocrine therapy resistance mechanisms 2.