PIN2/TERF1-interacting telomerase inhibitor 1, also known as PINX1, is a human gene. PINX1 is also known as PIN2 interacting protein 1. PINX1 is a telomerase inhibitor and a possible tumor suppressor. Interactions PINX1 has been shown to interact with MCRS1, TERF1 and telomerase reverse transcriptase. Structure There are two known variants of PINX1. The second variant “lacks an exon in the 3’ coding region which results in a frameshift compared to variant 1. The encoded isoform is shorter and has a distinct C-terminus compared to isoform 1.” There are three PINX1 cDNA clones. The longest one encodes a 328 amino acid 45kDa protein which contains an N-terminal Gly-rich patch and a C-terminal TID domain (telomerase inhibitory domain). The TRF1 binding domain is in the C-terminal 75 amino acids of PINX1. Mouse PINX1 is 74% identical to human PINX1. In other eukaryotes, including yeast, there is an overall 50% similarity to human PINX1. Function Over-expression of PINX1 results in decreased telomerase activity, telomere shortening, and induction of crisis. Reduction of PINX1 leads to an increase in telomerase activity and elongation of telomeres. PINX1 differs from other proteins that regulate telomere length in that it acts on telomerase while other proteins adjust telomere length without affecting telomerase activity. The PINX1 budding yeast orthologue Gnop1 inhibits telomerase by isolating the uncomplexed TERT protein so that it cannot associate with the telomerase template RNA, which prevents telomerase from being assembled. However, in humans, PINX1 impedes already assembled telomerase. PINX1 binds to N-terminus of hTERT and binds to hTR in the presence of hTERT. PINX1 binding to hTR “is correlated to the repressive function of PINX1 on telomerase, implying that the mode of enzyme telomerase inhibition by PINX1 may involve an associated with hTR....The effect of hPINX1 on telomerase appears to be exclusive of the G-patch region and is mediated instead by the C terminus of the protein. This suggests that hPINX1 may have functionally separable cellular effects in which the N terminus is involved in RNA processing via the G-patch, and the C terminus is involved in telomere dynamics.” It is suggested that “PINX1 represses telomerase activity in vivo by binding to the assembled hTERT-hTR complex.” The TID domain of PINX1 is likely what binds to hTERT. In cells, full-length PINX1 is not as strong as just the TID domain at inhibiting telomerase. This may be due to full-length PINX1 being subject to “endogenous