UBAP2 (ubiquitin associated protein 2) is a versatile ubiquitin-binding protein that plays critical roles in transcriptional regulation and cellular stress responses. Its primary function involves recruiting ubiquitination machinery to RNA polymerase II for degradation when transcription-coupled nucleotide excision repair fails to resolve DNA damage, serving as a human ortholog of yeast Def1 in the 'last resort' pathway 1. UBAP2 contains intrinsically disordered regions that enable phase separation, facilitating purinosome assembly during cellular stress by binding to K6-polyubiquitinated PAICS, thereby enhancing de novo purine synthesis efficiency 2. The protein also contributes to cancer biology through multiple mechanisms: it promotes hepatocellular carcinoma radioresistance by degrading the tumor suppressor SLC27A5 via the ubiquitin-proteasome system, leading to decreased homologous recombination gene RAD51 3. Additionally, UBAP2 is highly expressed in melanoma where it supports constitutive purinosome formation essential for tumor cell proliferation and viability 2. These findings establish UBAP2 as a key regulator linking ubiquitin signaling to transcriptional stress responses and metabolic reprogramming in both normal cellular homeostasis and cancer progression.