{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTelomerase‐associated protein 1 (TEP1) is a constitutive component of the human telomerase complex. Functional studies have shown that, unlike its catalytic subunit hTERT that fluctuates with telomerase activity, TEP1 (along with other non‐catalytic subunits) is stably expressed and assembled into the active holoenzyme, suggesting it plays a structural and assembly role essential for full telomerase function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in telomerase, TEP1 contributes to telomere maintenance through interactions in alternative lengthening of telomere (ALT) pathways. Research in ALT‐utilizing cells has demonstrated that TEP1 directly binds to the BLM helicase—along with other factors such as HSP90 and TOPOIIα—to modulate its helicase activity specifically on telomeric DNA substrates. This substrate‐selective regulation underscores TEP1’s involvement in preserving telomere integrity via non‐telomerase mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTEP1 is also a key component of vault ribonucleoprotein particles that have been implicated in cellular processes such as migration and multidrug resistance. In studies of ovarian and other cancers, while TEP1 mRNA levels are found to be reduced in tumor samples relative to normal tissue, paradoxically the protein levels increase in higher‐grade tumors—a pattern that suggests significant post‐transcriptional regulation. Moreover, in cancer cell models, TEP1, in concert with other vault proteins, has been linked to enhanced cell proliferation, migration, and resistance to chemotherapeutic agents."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic association studies further implicate TEP1 in disease susceptibility. In a study of male infertility, specific TEP1 polymorphisms were found to be positively associated with an increased risk of infertility. Additional investigations into cancer genetics have revealed that certain single‐nucleotide variants in TEP1 are linked to elevated risks of stomach cancer and hepatocellular carcinoma, although not all studies (for example, one in hepatocellular carcinoma) have confirmed these associations. Collectively, these findings suggest that genetic variations affecting TEP1 may influence telomere biology and thereby modulate disease risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, emerging evidence indicates that TEP1 expression can be modulated by non‐coding RNAs in pathological conditions such as liver fibrosis. A recent study using a circular RNA (hsa_circ_0004018) found that it acts as a sponge for hsa‐miR‐660‐3p, a microRNA that targets TEP1. The resultant modulation of the hsa_circ_0004018/hsa‐miR‐660‐3p/TEP1 axis impacts the proliferation and activation of hepatic stellate cells, thus contributing to the progression of liver fibrogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Joseph Tung-Chieh Chang, Yin-Ling Chen, Huei-Ting Yang, et al. 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