RUVBL1, also known as TIP49 or Pontin, is a protein that belongs to the AAA+ ATPase family. It forms a complex with RUVBL2, collectively known as RUVBL1/2, and functions as a co-chaperone in various cellular processes. These processes include chromatin remodeling, gene expression regulation, DNA replication, and the assembly and maturation of macromolecular complexes such as RNA polymerases and the mTOR complex. RUVBL1 has been implicated in cancer, with its overexpression associated with poor survival rates in various types of tumors. In non-small cell lung cancer (NSCLC), RUVBL1/2 ATPase activity is required for DNA replication and radioresistance, suggesting that inhibiting this activity could potentially increase the effectiveness of radiation therapy. Recent research has shown that RUVBL1 is involved in the regulation of the non-homologous end joining (NHEJ) pathway, which is a critical DNA repair mechanism. In head and neck squamous cell carcinoma (HNSCC), RUVBL1 is amplified and overexpressed, promoting proliferation and inhibiting the differentiation program. It plays a role in incorporating the histone variant H2AZ into chromatin, thereby regulating the transcription of key genes involved in differentiation, cancer cell proliferation, and invasion. Furthermore, RUVBL1 has been shown to correlate with the expression of molecular chaperones in hepatocellular carcinoma (HCC), and its activity is required for the stress response mediated by HSF1 (heat shock factor 1).