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Ovid Embase, Ovid Medline, Web of Science, and Cochrane Central were searched from inception through October 14, 2024, for human studies in English reporting familial NPH cases, genetic variants associated with NPH, and associations with other neurogenetic disorders and exploring transcriptomics. Studies on secondary, obstructive, and congenital hydrocephalus were excluded, and findings were reported narratively. Of 2562 titles and abstracts screened, 56 met inclusion criteria, predominantly involving European populations. More than 30 familial cases were identified, and two cohorts found that 10%\u201316% of patients with NPH had relatives with NPH symptoms. Whole\u2010genome\/exome sequencing, copy\u2010number variant analyses, and genome\u2010wide association studies showed risk variants enriched in NPH cohorts in or near <jats:italic>CFAP43<\/jats:italic>, <jats:italic>SFMBT1<\/jats:italic>, <jats:italic>CWH43<\/jats:italic>, <jats:italic>AK9<\/jats:italic>, <jats:italic>RXFP2<\/jats:italic>, <jats:italic>PRKD1<\/jats:italic>, <jats:italic>HAVCR1<\/jats:italic>, <jats:italic>OTOG<\/jats:italic>, <jats:italic>MYO7A<\/jats:italic>, <jats:italic>NOTCH1<\/jats:italic>, <jats:italic>SPG11<\/jats:italic>, <jats:italic>MYH13<\/jats:italic>, <jats:italic>FOXJ1<\/jats:italic>, <jats:italic>AMZ1\/GNA12<\/jats:italic>, and <jats:italic>C16orf95<\/jats:italic>, alongside protective variants near <jats:italic>SLCO1A2<\/jats:italic> and <jats:italic>MLLT10<\/jats:italic>. These genes are associated with blood\u2010brain and blood\u2013cerebrospinal fluid barriers, cilia, and ependymal function. In addition, higher rates of pathological <jats:italic>C9orf72<\/jats:italic> repeat expansions were observed in an NPH cohort compared with controls. NPH was also more prevalent in frontotemporal dementia cohorts without this expansion and co\u2010occurred with myotonic dystrophy type 1 in several cases. Despite heterogeneity in outcome measures, this review highlights the genetic contribution to NPH risk. Future research should encourage collaborations for big data generation, identify genetic variants addressing diversity, and integrate clinical, environmental, and shunt\u2010response data. \u00a9 2025 The Author(s). <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p>","DOI":"10.1002\/mds.30206","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T09:40:15Z","timestamp":1745401215000},"page":"1233-1247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Genetic Risk Factors in Normal Pressure Hydrocephalus: What We Know and What Is Next"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5555-7741","authenticated-orcid":false,"given":"Camila C.","family":"Piccinin","sequence":"first","affiliation":[{"name":"Center for Neurological Restoration Neurological Institute, Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saar","family":"Anis","sequence":"additional","affiliation":[{"name":"Center for Neurological Restoration Neurological Institute, Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeryl Ritzi T.","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences, St. Luke's Medical Center  Quezon City Philippines"},{"name":"University of the East Ramon Magsaysay Memorial Medical Center  Quezon City Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8669-284X","authenticated-orcid":false,"given":"Philippe A.","family":"Salles","sequence":"additional","affiliation":[{"name":"Center for Movement Disorders, CETRAM  Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1649-7854","authenticated-orcid":false,"given":"Henry Mauricio","family":"Chaparro\u2010Solano","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine Cleveland Clinic Lerner College of Medicine, Case Western Reserve University  Cleveland Ohio USA"},{"name":"Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic Foundation  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avery","family":"Kundrick","sequence":"additional","affiliation":[{"name":"Center for Neurological Restoration Neurological Institute, Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shelley","family":"Ivary","sequence":"additional","affiliation":[{"name":"Education Institute, Floyd D. 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