Pinin, desmosome-associated protein (PNN) (PNN)

Pinin, encoded by the PNN gene, is a versatile phosphoprotein that serves dual roles in the nucleus and at the cell-cell interface. It was originally characterized as a desmosome-associated protein that stabilizes epithelial cell-cell adhesion by anchoring intermediate filaments to the desmosomal plaque. In the nucleus, Pinin localizes to nuclear speckles and functions as a transcriptional coactivator and a peripheral component of the exon junction complex (EJC), where it modulates alternative pre-mRNA splicing and mRNA export. It is particularly known for its ability to bind C-terminal binding proteins (CtBPs) and relieve the repression of the E-cadherin promoter, thereby maintaining epithelial identity. In clinical oncology, Pinin is frequently overexpressed and acts as an oncogenic driver in multiple malignancies, including prostate, ovarian, colorectal, and renal cell carcinomas, where it promotes epithelial-mesenchymal transition (EMT), proliferation, and metastasis. While it is considered an emerging therapeutic target, no direct small-molecule inhibitors have reached clinical use to date, and its involvement in fundamental splicing processes necessitates careful evaluation of potential systemic toxicity.

Other names

MemASDK3DRS proteinDesmosome-associated proteinDRSPMelanoma metastasis clone A protein140 kDa nuclear and cell adhesion-related phosphoproteinDomain-rich serine protein