Telomeric repeat-binding factor 2-interacting protein (TERF2IP, also known as RAP1) is a component of the Shelterin Complex, a multi-protein complex that binds and organizes telomeres into T-loop structures to prevent them from being recognized by the cell as DNA double stranded breaks. The Shelterin Complex is composed of TERF2IP, TIN2 and TPP2 proteins, in addition to three DNA binding proteins that function to recruit the complex to telomeres: TRF1 and TRF2 bind double-stranded TTAGGG repeats found at telomeres, while the POT1 protein binds single-stranded TTAGGG repeats found at the very end of the telomeres. Together, these proteins function to protect telomeres and ensure proper replication and processing of chromosome ends. Recent studies have shown that TERF2IP is dispensable for maintenance of telomere length, organization of telomeric chromatin, and regulation of telomeric transcription. However, TERF2IP is required for inhibition of homology-directed repair (HDR), which can create undesirable telomeric sister chromatid exchange. In addition to its role in telomere maintenance, TERF2IP is also found in the cytoplasm, where it functions as an IkB kinase (IKK) adaptor protein and regulates NF-kB-dependent gene expression. TERF2IP forms a complex with IKKs and is critical for proper recruitment of IKKs to and activation of the p65 subunit of NF-kB. Elevated levels of TERF2IP have been found in breast cancer cells with NF-kB hyperactivity, and knockdown of TERF2IP sensitizes these cells to apoptosis, further identifying TERF2IP as a potential cancer therapeutic target.