{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:17:08Z","timestamp":1792793828668,"version":"4.5.0"},"reference-count":123,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Haploinsufficiency disorders are genetic diseases caused by reduced gene expression, leading to developmental, metabolic, and tumorigenic abnormalities. The dosage-sensitive Retinoic Acid Induced 1 (RAI1) gene, located within the 17p11.2 region, is central to the core features of Smith\u2013\u2013Magenis syndrome (SMS) and Potocki\u2013\u2013Lupski syndrome (PTLS), caused by the reciprocal microdeletions and microduplications of this region, respectively. SMS and PTLS present contrasting phenotypes. SMS is characterized by severe neurobehavioral manifestations, sleep disturbances, and metabolic abnormalities, and PTLS shows milder features. Here, we detail the molecular functions of RAI1 in its wild-type and haploinsufficiency conditions (RAI1+\/\u2212), as studied in animal and cellular models. RAI1 acts as a transcription factor critical for neurodevelopment and synaptic plasticity, a chromatin remodeler within the Histone 3 Lysine 4 (H3K4) writer complex, and a regulator of faulty 5\u2032-capped pre-mRNA degradation. Alterations of RAI1 functions lead to synaptic scaling and transcriptional dysregulation in neural networks. This review highlights key molecular mechanisms of RAI1, elucidating its role in the interplay between genetics and phenotypic features and summarizes innovative therapeutic approaches for SMS. These data provide a foundation for potential therapeutic strategies targeting RAI1, its mRNA products, or downstream pathways.<\/jats:p>","DOI":"10.3390\/ijms26146667","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T13:44:19Z","timestamp":1752241459000},"page":"6667","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["RETRACTED: Retinoic Acid Induced 1 and Smith\u2013Magenis Syndrome: From Genetics to Biology and Possible Therapeutic Strategies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1936-5284","authenticated-orcid":false,"given":"Jasmine","family":"Covarelli","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, Piazza L. Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Vinciarelli","sequence":"additional","affiliation":[{"name":"Medical Genetics and Rare Disease Unit, Maternal-Infantile Department, S. Maria della Misericordia Hospital, 06132 Perugia, Italy"},{"name":"Department of Translational Medicine and for Romagna, University of Ferrara, Via L. Borsari 46, 44121 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Mirarchi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, Piazza L. Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Prontera","sequence":"additional","affiliation":[{"name":"Medical Genetics and Rare Disease Unit, Maternal-Infantile Department, S. Maria della Misericordia Hospital, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3114-8812","authenticated-orcid":false,"given":"Cataldo","family":"Arcuri","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Perugia, Piazza L. Severi 1, 06132 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1136\/jmg.31.2.89","article-title":"The Molecular Basis of Genetic Dominance","volume":"31","author":"Wilkie","year":"1994","journal-title":"J. Med. 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