PHF5A (PHD finger protein 5A) is a highly conserved nuclear protein that functions as a critical component of the U2 small nuclear ribonucleoprotein (snRNP) complex in the spliceosome 1. As part of the SF3B subcomplex within the 17S U2 snRNP, PHF5A directly participates in early spliceosome assembly and mediates recognition of intron branch sites during pre-mRNA splicing. The protein acts as a bridge between splicing factors and ATP-dependent helicases, specifically interacting with splicing proteins U2AF1 and SFRS5 through its C-terminal region, while its N-terminal domain associates with helicases EP400 and DDX1 2. Beyond its splicing function, PHF5A serves as a transcriptional regulator and is involved in maintaining stem cell features in cancer cells through interactions with DDX3 and regulation of NANOG expression 3. PHF5A shows tissue-specific expression patterns, particularly in muscle development during embryogenesis 1. Clinically, PHF5A has significant disease relevance as de novo variants cause developmental disorders with craniofacial abnormalities and developmental delay 4. The protein is overexpressed in various cancers including pancreatic, colorectal, and esophageal cancers, where it promotes tumor progression through multiple mechanisms including regulation of alternative splicing and stabilization of oncogenic proteins like VEGFA 567.