PHF14 (PHD finger protein 14) is a nuclear histone-binding protein that functions as an epigenetic regulator with critical roles in development and disease. Primary function: PHF14 reads unmodified histone H3 through its integrated PHD1-ZnK-PHD2 cassette via bipartite recognition, preferentially binding the N-terminal and middle regions of histone H3 1. The protein suppresses PDGFRA expression and represses proliferation-associated genes like CDKN1A/p21 by modulating histone H3 lysine methylation patterns 2. Mechanism: PHF14 forms functional complexes with chr7 regulators including HMG20A and components of the TCF20/PHF14 complex, modulating TGFβ and Hippo signaling pathways to regulate epithelial-mesenchymal plasticity 3. PHF14 participates in DNA damage response complexes through interactions with KIF4A and BRCA2/Rad51, contributing to genomic stability 4. Disease relevance: PHF14 knockout causes neonatal lethality due to respiratory failure and lung development defects 5. Mutations in PHF14 are identified in neurocytomas (14% of cases) and colorectal cancer (18% mutation rate), with loss-of-function mutations increasing cellular proliferation 2, 4. Dysregulated circPHF14 biogenesis promotes pancreatic ductal adenocarcinoma growth via Wnt/β-catenin pathway activation 6. Clinical significance: PHF14 mutations are linked to neurodevelopmental disorders through the TCF20/PHF14 chr7 complex 7. High PHF14 expression correlates with poor cancer prognosis across multiple tumor types and immune infiltration patterns 8.