RAD23A is a multifunctional nucleotide excision repair (NER) protein that serves as a ubiquitin receptor facilitating proteasomal degradation of ubiquitinated substrates. Its primary role involves coordinating DNA damage repair through interactions with NER machinery and Y-family DNA polymerases 1. RAD23A functions in substrate structure-dependent proteasomal degradation, with well-folded substrates requiring RAD23A and the p97 ATPase, while unstructured substrates can bypass these accessory factors 2. Beyond DNA repair, RAD23A regulates proteostasis in neurodegenerative disease contexts. Reduction of RAD23A decreases insoluble TDP-43 aggregates and improves survival and locomotor function in TDP-43 proteinopathy models 34, suggesting it acts as a modifier of protein aggregation pathology. In cancer, RAD23A expression is upregulated in niraparib-resistant ovarian cancer through lactate-induced histone H4K12 lactylation activating super-enhancers, and RAD23A inhibition restores drug sensitivity 5. RAD23A also functions in prognostic assessment, with elevated expression associated with T cell exhaustion in osteosarcoma correlating with worse prognosis and reduced immunotherapy response 6. Additionally, RAD23A participates in UV response and DNA repair alongside RAD23B, with differential contributions to cell survival after ultraviolet irradiation 7. Clinically, RAD23A represents a potential therapeutic target for niraparib-resistant ovarian cancer and TDP-43-related neurodegenerative diseases.