Current insights into PHF14: molecular features and functional roles.

Plant Homeodomain Finger Protein 14 (PHF14) is a known epigenetic regulator involved in chromatin-mediated gene regulation. PHF14 belongs to the plant homeodomain (PHD) family, and possesses four PHD zinc-finger domains. The N-terminal PHD1 and PHD2 domain of PHF14 mediate histone recognition through specific PHD1-ZnK-PHD2 (PZP) cassettes and thereby contribute to the regulation of transcriptional activation and gene silencing. PHF14 plays a role in regulating essential cellular processes such as the cell cycle, mesenchymal proliferation, DNA damage response, and B-cell proliferation. Genetic variants of PHF14 have been identified across multiple clinical conditions, underscoring its physiological and pathologic relevance. Over the past 5 years, PHF14 has garnered substantial attention for its dysregulation or sequence variation associated with various cancers. PHF14-mediated interactions are implicated in neurodevelopmental disorders and also contribute to lung and renal fibrosis, as well as Dandy-Walker syndrome, underscoring its role in diverse pathological conditions. This review summarizes current knowledge on PHF14 structure, interaction partners, molecular functions, associated signaling pathways, and roles in diseases.