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A wealth of data in the last decade has unraveled disturbances of lipid droplet (LD) biogenesis, maturation, turnover and contact sites in cellular and animal models with perturbed expression and function of HSP proteins. As ubiquitous organelles that segregate neutral lipid into a phospholipid monolayer, LDs are at the cross-road of several processes including lipid metabolism and trafficking, energy homeostasis, and stress signaling cascades. However, their role in brain cells, especially in neurons remains enigmatic. Here, we review experimental findings linking LD abnormalities to defective function of proteins encoded by HSP genes, and discuss arising questions in the context of the pathogenesis of HSP.<\/jats:p>","DOI":"10.3389\/fmolb.2021.673977","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T04:16:56Z","timestamp":1620620216000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Lipid Droplets in the Pathogenesis of Hereditary Spastic Paraplegia"],"prefix":"10.3389","volume":"8","author":[{"given":"Nimesha","family":"Tadepalle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Rugarli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,5,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.1083\/jcb.201609033","article-title":"Defects in ER-Endosome Contacts Impact Lysosome Function in Hereditary Spastic Paraplegia","volume":"216","author":"Allison","year":"2017","journal-title":"J. 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