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Although this disease causes multisystemic symptoms, it is mainly characterised by myopathy or diseased muscles, which includes muscle weakness, atrophy, and myotonia, severely affecting the lives of patients worldwide. On a molecular level, DM1 is caused by an expansion of CTG repeats in the 3\u2032 untranslated region (3\u2032UTR) of the <jats:italic>DM1 Protein Kinase<\/jats:italic> (<jats:italic>DMPK<\/jats:italic>) gene which become pathogenic when transcribed into RNA forming ribonuclear foci comprised of auto complementary CUG hairpin structures that can bind proteins. This leads to the sequestration of the muscleblind\u2010like (MBNL) family of proteins, depleting them, and the abnormal stabilisation of CUGBP Elav\u2010like family member 1 (CELF1), enhancing it. Traditionally, DM1 research has focused on this RNA toxicity and how it alters MBNL and CELF1 functions as key splicing regulators. However, other proteins are affected by the toxic <jats:italic>DMPK<\/jats:italic> RNA and there is strong evidence that supports various signalling cascades playing an important role in DM1 pathogenesis. Specifically, the impairment of protein kinase B (AKT) signalling in DM1 increases autophagy, apoptosis, and ubiquitin\u2013proteasome activity, which may also be affected in DM1 by AMP\u2010activated protein kinase (AMPK) downregulation. AKT also regulates CELF1 directly, by affecting its subcellular localisation, and indirectly as it inhibits glycogen synthase kinase 3 beta (GSK3\u03b2), which stabilises the repressive form of CELF1 in DM1. Another kinase that contributes to CELF1 mis\u2010regulation, in this case by hyperphosphorylation, is protein kinase C (PKC). Additionally, it has been demonstrated that fibroblast growth factor\u2010inducible 14 (Fn14) is induced in DM1 and is associated with downstream signalling through the nuclear factor \u03baB (NF\u03baB) pathways, associating inflammation with this disease. Furthermore, MBNL1 and CELF1 play a role in cytoplasmic processes involved in DM1 myopathy, altering proteostasis and sarcomere structure. Finally, there are many other elements that could contribute to the muscular phenotype in DM1 such as alterations to satellite cells, non\u2010coding RNA metabolism, calcium dysregulation, and repeat\u2010associated non\u2010ATG (RAN) translation. This review aims to organise the currently dispersed knowledge on the different pathways affected in DM1 and discusses the unexplored connections that could potentially help in providing new therapeutic targets in DM1 research.<\/jats:p>","DOI":"10.1111\/brv.12674","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T03:47:51Z","timestamp":1606967271000},"page":"716-730","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":82,"title":["The hallmarks of myotonic dystrophy type 1 muscle dysfunction"],"prefix":"10.1111","volume":"96","author":[{"given":"Lauren L.","family":"Ozimski","sequence":"first","affiliation":[{"name":"Translational Genomics Group Incliva Health Research Institute  Avda. Men\u00e9ndez Pelayo 4 acc. 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