PHF1 (PHD finger protein 1) is a polycomb-like protein that functions as a chr6 reader and transcriptional regulator through its association with the Polycomb repressive complex 2 (PRC2) 1. As a member of the PRC2.1 subcomplex, PHF1 plays a crucial role in targeting PRC2 to its genomic sites and regulating gene expression through epigenetic mechanisms 1. PHF1 is frequently involved in oncogenic gene fusions in soft tissue tumors, particularly ossifying fibromyxoid tumors (OFMTs), where it forms fusions with multiple partners including EP400, MEAF6, TFE3, FOXR1, and FOXR2 234. These fusions cause extensive transcriptional upregulation and altered chr6 accessibility, contributing to tumor development through dysregulated Wnt signaling and H3K27me3-mediated gene regulation 2. PHF1 fusions are also found in endometrial stromal sarcomas, such as the novel MBTD1-PHF1 fusion, which mediates tumorigenesis through aberrant transcriptional repression 5. Beyond cancer, PHF1 has been implicated in Alzheimer's disease pathology, where it interacts with phosphorylated tau in neurofibrillary tangles 6. The clinical significance of PHF1 lies in its utility as a diagnostic marker for soft tissue tumors and its potential as a therapeutic target in both cancer and neurodegenerative diseases.