Human Telomeric Repeat Binding Factor 2 Interacting Protein (TERF2IP) Protein

Background

TERF2IP, also known as RAP1, is a key component of the shelterin complex that interacts with TERF2 to regulate telomere protection and maintenance. While TERF2IP does not directly bind to telomeric DNA, it associates with TERF2 to stabilize telomeric t-loops, preventing chromosome end fusions and inappropriate activation of DNA damage signaling pathways. TERF2IP is also involved in non-telomeric functions, including transcriptional regulation, NF-κB signaling, and metabolic control, highlighting its broader cellular roles. It is widely expressed in proliferative tissues, where it maintains telomere length homeostasis and protects chromosome ends during replication. Dysregulation of TERF2IP has been linked to premature aging, genomic instability, and cancer, where altered shelterin function results in telomere dysfunction and increased susceptibility to DNA damage. Functional studies show that TERF2IP loss leads to telomere deprotection, chromosomal instability, and activation of p53-mediated cell cycle arrest, underscoring its essential role in telomere maintenance, genomic stability, and transcriptional regulation.