USP45 is a deubiquitinating enzyme with diverse cellular functions critical for DNA repair, cell migration, and photoreceptor maintenance. The protein catalyzes the removal of ubiquitin chains from multiple substrates, including ERCC1, SPDL1, and Coronin 1B 123. In DNA repair, USP45 deubiquitinates ERCC1, promoting its recruitment to UV-induced damage sites and facilitating nucleotide excision repair 1. The enzyme also regulates autophagy by deubiquitinating and stabilizing Coronin 1B, which controls actin dynamics and lysosomal function 3. USP45 demonstrates tumor suppressor activity in melanoma through stabilization of MRGPRF 4, while paradoxically promoting oncogenesis in ovarian cancer via snail deubiquitination 5. In photoreceptor biology, USP45 is essential for retinal function and development, with biallelic mutations causing Leber congenital amaurosis 19 (LCA19) 6. The enzyme localizes to photoreceptor inner segments, and its knockout in mice produces electroretinography abnormalities resembling human LCA patients 6. USP45 also facilitates cell migration through deubiquitination of SPDL1 2. These findings establish USP45 as a multifunctional deubiquitinase with context-dependent roles in cellular homeostasis, DNA repair, and disease pathogenesis.