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This narrative review synthesizes the literature through May 2025, examining clinical behavior, imaging, pathology, hereditary syndromes, and the molecular drivers of ONSMs, with particular emphasis on NF2, SMARCB1, TRAF7, and recent copy-number and methylation studies. Classic sporadic ONSMs seldom exhibit loss of chromosome 22q. However, somatic NF2 alterations and occasional changes in chromatin-remodeling genes still converge on Hippo pathway output (Yes-associated protein\/transcriptional coactivator with PDZ-binding motif (YAP\/TAZ)-driven transcriptional activity), phosphoinositide 3-kinase\u2013protein kinase B (PI3K\u2013AKT), and MAPK signaling. Emerging multi-omics data indicate that optic nerve tumors represent a molecularly distinct subset within the meningioma spectrum. This finding may explain the associated characteristically indolent growth and favorable response to conformal radiotherapy. Genotyping refines risk stratification: early NF2 testing is warranted in children and in bilateral or atypical presentations, enabling timely surveillance and genetic counseling. While fractionated stereotactic radiotherapy remains the mainstay of therapy, pathway-targeted and gene-replacement strategies developed for NF2-associated tumors may soon expand therapeutic options. Given the site-specific diagnostic and functional constraints of peri-optic tumors, larger collaborative cohorts and genotype-guided trials are essential to translate these biological insights into precision care for patients with ONSMs.<\/jats:p>","DOI":"10.31083\/fbs46877","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T12:05:49Z","timestamp":1783425949000},"source":"Crossref","is-referenced-by-count":0,"title":["Looking at Optic Nerve Sheath Meningiomas Through Genetics\u2014From Clinic to Bench and Back Again"],"prefix":"10.31083","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":true,"given":"Marco","family":"Zeppieri","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy"},{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-876X","authenticated-orcid":true,"given":"Fabiana","family":"D\u2019Esposito","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, 94100 Enna, Italy"},{"name":"Imperial College Ophthalmic Research Group [ICORG] Unit, Imperial College, NW1 5QH London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":true,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5940-6177","authenticated-orcid":true,"given":"Marco","family":"Battista","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0118-4177","authenticated-orcid":true,"given":"Piero","family":"Barboni","sequence":"additional","affiliation":[{"name":"IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Studio Oculistico d\u2019Azeglio, 40123 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2073-3758","authenticated-orcid":true,"given":"Simonetta Gaia","family":"Nicolosi","sequence":"additional","affiliation":[{"name":"Eye Clinic, Catania University, Policlinico G. 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