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In humans, mutations in <jats:italic>CLN<\/jats:italic> genes cause a devastating form of neurodegeneration called neuronal ceroid lipofuscinosis (NCL), commonly known as Batten disease. Each <jats:italic>CLN<\/jats:italic> gene is associated with a specific subtype of the disease that differ from each other in severity and age of onset. The NCLs affect all ages and ethnicities worldwide but primarily affect children. The pathology underlying the NCLs is poorly understood, which has prevented the development of a cure or effective therapy for most subtypes of the disease. A growing body of literature supports the networking of <jats:italic>CLN<\/jats:italic> genes and proteins within cells, which aligns with the broadly similar cellular and clinical manifestations among the different subtypes of NCL. Here, all relevant literature is reviewed to provide a comprehensive overview of our current understanding of how <jats:italic>CLN<\/jats:italic> genes and proteins are networked in mammalian cells with an aim toward revealing new molecular targets for therapy development. Intriguingly, <jats:italic>CLN<\/jats:italic> gene and protein networking extends beyond the NCLs as recent work has linked several <jats:italic>CLN<\/jats:italic> genes and proteins to other forms of neurodegeneration such as Alzheimer's disease and Parkinson's disease. Thus, a deeper understanding of the pathways and cellular processes impacted by mutations in <jats:italic>CLN<\/jats:italic> genes will not only strengthen our knowledge of the pathological mechanisms underlying the NCLs but may also provide new insight into related forms of neurodegeneration.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15822-fig-0004-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1111\/jnc.15822","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T14:54:21Z","timestamp":1680792861000},"page":"643-659","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Recent insights into the networking of <i>CLN<\/i> genes and proteins in mammalian cells"],"prefix":"10.1111","volume":"165","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2606-6983","authenticated-orcid":false,"given":"Robert J.","family":"Huber","sequence":"first","affiliation":[{"name":"Department of Biology Trent University  Peterborough Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-36379-z"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12106"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3081-17.2018"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-011-8194-0"},{"key":"e_1_2_11_6_1","first-page":"4118","article-title":"A CLN6\u2010CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer","volume":"130","author":"Bajaj L.","year":"2020","journal-title":"The Journal of Clinical Investigation"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2021.03.020"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj1040601"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11101412"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(05)80908-8"},{"key":"e_1_2_11_11_1","first-page":"386","article-title":"Cerebral degeneration with symmetrical changes in the maculae in two members of a family","volume":"23","author":"Batten F. 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