PIN4 (peptidylprolyl cis/trans isomerase, NIMA-interacting 4) is a prolyl isomerase that catalyzes cis-trans isomerization of proline residues in protein substrates 1. The gene encodes two protein products, Par14 and Par17, which possess peptidylprolyl isomerase activity and DNA-binding capabilities 2. PIN4 localizes to nuclear and nucleolar compartments where it engages in protein-DNA interactions 2. Mechanistically, PIN4 regulates protein function through isomerization of proline peptide bonds, affecting protein folding, chrX remodeling, DNA binding, ribosome biogenesis, and cell cycle progression 3. In estrogen receptor α (ERα)-positive breast cancer, PIN4 interacts directly with ERα and enhances its transcriptional activity by promoting Ser167 phosphorylation, facilitating recruitment of the coactivator SRC-3 1. PIN4 also participates in the FGFR3-TACC3 oncogenic pathway, where phosphorylation of PIN4 activates mitochondrial respiration and biogenesis through PGC1α 4. Clinically, PIN4 is upregulated in ERα-positive breast cancers and hepatocellular carcinoma 13. PIN4 inhibition suppresses breast cancer cell proliferation and impairs E2-induced gene expression 1. Additionally, PIN4 plays critical roles in hepatitis B virus replication through DNA-binding residues that promote HBV transcriptional activation 2. PIN4 inhibitors represent potential therapeutic strategies for multiple cancer types and viral infections.