TPP1

TPP1, also called telomere protection protein 1, is a protein component of the shelterin complex that guards mammalian telomeres. It is encoded by the ACD gene in humans and is conserved across vertebrates. In shelterin, TPP1 forms a tight association with POT1; together they bind the single-stranded G-rich telomeric overhang and help cap chromosome ends.

TPP1 plays a dual role in telomere length maintenance and protection. Its interaction with POT1 promotes recruitment of telomerase to telomeres and stimulates telomerase processivity, enabling elongation of telomeric DNA. In addition, by stabilizing the POT1-DNA interaction and contributing to the architecture of shelterin, TPP1 helps prevent inappropriate DNA damage signaling at chromosome ends, reducing ATM/ATR pathway activation.

Disruptions to TPP1 function, whether by altered expression or mutation, can impair telomere maintenance and are studied in the context of telomere biology disorders and cancer. Research continues to define the precise domains responsible for POT1 binding, telomerase recruitment, and telomere protection, as well as the regulation of TPP1 by cellular signaling.

TPP1 is a well-conserved component in vertebrates and has been studied in human cells and mouse models. See also shelterin, POT1, telomerase, telomeres.