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Both TSC1 and TSC2 inhibit the mammalian target of rapamycin (mTOR) complexes pathway, which is crucial for cell proliferation, growth, and differentiation, and is stimulated by various energy sources and hormonal signaling pathways. Pathogenic variants in TSC1 and TSC2 lead to mTORC1 hyperactivation, producing benign tumours in multiple organs, including the brain and kidneys, and drug-resistant epilepsy, a typical sign of TSC. Brain tumours, sudden unexpected death from epilepsy, and respiratory conditions are the three leading causes of morbidity and mortality. Even though several therapeutic options are available for the treatment of TSC, there is further need for a better understanding of the pathophysiological basis of the neurologic and other manifestations seen in TSC, and for novel therapeutic approaches. This review provides an overview of the main current therapies for TSC and discusses recent studies highlighting the repurposing of approved drugs and the emerging role of novel targets for future drug design.<\/jats:p>","DOI":"10.3390\/biom14091190","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T03:36:38Z","timestamp":1727062598000},"page":"1190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Therapeutic Approaches to Tuberous Sclerosis Complex: From Available Therapies to Promising Drug Targets"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-5125","authenticated-orcid":false,"given":"Elena","family":"Conte","sequence":"first","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-8490","authenticated-orcid":false,"given":"Brigida","family":"Boccanegra","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Dinoi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8644-8847","authenticated-orcid":false,"given":"Michael","family":"Pusch","sequence":"additional","affiliation":[{"name":"Institute of Biophysics, National Research Council, 16149 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-7341","authenticated-orcid":false,"given":"Annamaria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Liantonio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-5350","authenticated-orcid":false,"given":"Paola","family":"Imbrici","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106884","DOI":"10.1016\/j.phrs.2023.106884","article-title":"Paradigm shift in the treatment of tuberous sclerosis: Effectiveness of everolimus","volume":"195","author":"Previtali","year":"2023","journal-title":"Pharmacol. 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