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sequences that can form diverse topologies based on the arrangement of their four strands. G4s have attracted attention for their potential roles in various biological processes and human diseases. In this review, we focus on the G4 structures formed by human telomeric sequences, (GGGTTA)n, and the hexanucleotide repeat expansion, (GGGGCC)n, in the first intron region of the chromosome 9 open reading frame 72 (C9orf72) gene, highlighting their structural diversity and biological significance. Human telomeric G4s play crucial roles in telomere retention and gene regulation. In particular, we provide an in-depth summary of known telomeric G4s and focus on our recently discovered chair-type conformation, which exhibits distinct folding patterns. The chair-type G4s represent a novel folding pattern with unique characteristics, expanding our knowledge of telomeric G4 structural diversity and potential biological functions. Specifically, we emphasize the G4s formed by the (GGGGCC)n sequence of the C9orf72 gene, which represents the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The thorough structural analysis in this review advances our comprehension of the disease mechanism and provides valuable insights into developing targeted therapeutic strategies in ALS\/FTD.<\/jats:p>","DOI":"10.3390\/ijms26041591","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T09:05:42Z","timestamp":1739437542000},"page":"1591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["G-Quadruplex Structures Formed by Human Telomere and C9orf72 GGGGCC Repeats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2478-1502","authenticated-orcid":false,"given":"Bing","family":"Yan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Molecular Neuroscience, Institute for Advanced Study, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0721-4867","authenticated-orcid":false,"given":"Monica Ching","family":"Suen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Neuroscience, Institute for Advanced Study, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naining","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Neuroscience, Institute for Advanced Study, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China"},{"name":"HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5364-2136","authenticated-orcid":false,"given":"Chao","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changdong","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Neuroscience, Institute for Advanced Study, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China"},{"name":"HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Neuroscience, Institute for Advanced Study, Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China"},{"name":"HKUST Shenzhen Research Institute, Hi-Tech Park, Nanshan, Shenzhen 518057, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","first-page":"203","article-title":"Role of Alkali Metal Ions in G-Quadruplex Nucleic Acid Structure and Stability","volume":"16","author":"Largy","year":"2016","journal-title":"Met. 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