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Mutations in the <jats:italic>ELOVL4<\/jats:italic> gene cause several distinct neurodegenerative diseases including Stargardt-like macular dystrophy (STGD3), spinocerebellar ataxia 34 (SCA34), and a neuro-ichthyotic syndrome with severe seizures and spasticity, as well as erythrokeratitis variabilis (EKV), a skin disorder. However, the relationship between <jats:italic>ELOVL4<\/jats:italic> mutations, its VLC-PUFA and VLC-SFA products, and specific neurological symptoms remains unclear. We generated a knock-in rat line (SCA34-KI) that expresses the 736T&gt;G (p.W246G) form of <jats:italic>ELOVL4<\/jats:italic> that causes human SCA34. Lipids were analyzed by gas chromatography and mass spectrometry. Retinal function was assessed using electroretinography. Retinal integrity was assessed by histology, optical coherence tomography, and immunolabeling. Analysis of retina and skin lipids showed that the W246G mutation selectively impaired synthesis of VLC-SFA, but not VLC-PUFA. Homozygous SCA34-KI rats showed reduced ERG a- and b-wave amplitudes by 90\u00a0days of age, particularly for scotopic responses. Anatomical analyses revealed no indication of neurodegeneration in heterozygote or homozygote SCA34-KI rats out to 6\u20137\u00a0months of age. These studies reveal a previously unrecognized role for VLC-SFA in regulating retinal function, particularly transmission from photoreceptors to the inner retina, in the absence of neurodegeneration. Furthermore, these findings suggest that the tissue specificity and symptoms associated with disease-causing <jats:italic>ELOVL4<\/jats:italic> mutations likely arise from selective differences in the ability of the mutant ELOVL4 enzymes to support synthesis of VLC-PUFA and\/or VLC-SFA.<\/jats:p>","DOI":"10.1007\/s12035-020-02052-8","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T09:40:03Z","timestamp":1597138803000},"page":"4735-4753","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The Elovl4 Spinocerebellar Ataxia-34 Mutation 736T&gt;G (p.W246G) Impairs Retinal Function in the Absence of Photoreceptor Degeneration"],"prefix":"10.1007","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1920-915X","authenticated-orcid":false,"given":"Martin-Paul","family":"Agbaga","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan A.","family":"Stiles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard S.","family":"Brush","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael T.","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adeline","family":"Machalinski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth L.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1568-0611","authenticated-orcid":false,"given":"David M.","family":"Sherry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,11]]},"reference":[{"key":"2052_CR1","doi-asserted-by":"crossref","first-page":"12843","DOI":"10.1073\/pnas.0802607105","volume":"105","author":"MP Agbaga","year":"2008","unstructured":"Agbaga MP, Brush RS, Mandal MN, Henry K, Elliott MH, Anderson RE (2008) Role of Stargardt-3 macular dystrophy protein (ELOVL4) in the biosynthesis of very long chain fatty acids. 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