PHF12 (PHD finger protein 12) functions as a transcriptional repressor and key scaffolding subunit of SIN3 chr17-remodeling complexes. As a core component of these complexes, PHF12 stabilizes the assembly by contacting each subunit domain and recruits the H3 histone tail to serve as the substrate receptor 1. The SIN3B complex containing PHF12 represses transcription by recognizing H3K27ac marks and recruiting histone deacetylase activity to counteract histone acetyltransferase activity, thereby mitigating histone acetylation and RNA polymerase II progression at transcribed regions 1. PHF12 may also function in a SIN3A-independent manner through recruitment of TLE5 complexes 2. Clinically, PHF12 dysregulation is implicated in multiple malignancies. In non-small cell lung cancer, PHF12 is upregulated and promotes tumorigenesis by transcriptionally regulating HDAC1 expression and activating EGFR/AKT signaling 3. In lung squamous cell carcinoma, PHF12 upregulation driven by lncRNA RP11-116G8.5 promotes cancer cell proliferation and invasion 4. PHF12 suppression by MYC-mediated m6A modifications also contributes to MYC-driven lymphoma progression 5. Additionally, PHF12 variants are associated with age-related macular degeneration and intraocular pressure regulation 67, and PHF12 expression patterns show diagnostic potential for prostate cancer detection 8.