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USP1 (ubiquitin‑specific protease 1) is a deubiquitinating enzyme crucial for DNA damage repair, cell cycle regulation, and protein homeostasis. Its catalytic efficiency is markedly enhanced by UAF1 (USP1‑associated factor 1), a cofactor that stabilizes USP1 and directs it to nuclear substrates. Together, the USP1–UAF1 complex removes ubiquitin from key proteins such as PCNA and FANCD2, maintaining genomic stability and influencing cancer development, making it a potential therapeutic target in oncology.