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As a class with pleiotropic effects, recent efforts have centred on discerning specific ceramide species and their effects on atopic dermatitis, obesity, type 2 diabetes, and cardiovascular diseases. This delineation has allowed the identification of disease biomarkers, with long acyl chain ceramides such as C16- and C18-ceramides linked to metabolic dysfunction and cardiac function decline, while ultra-long acyl chain ceramides (&gt;25 carbon acyl chain) were reported to be essential for maintaining a functional skin barrier. Given the intricate link between free fatty acids with ceramides, especially the de novo synthetic pathway, intracellular lipid droplet formation is increasingly viewed as an important mechanism for preventing accumulation of toxic ceramide species. Here, we review recent reports of various ceramide species involved in skin abnormalities and metabolic diseases, and we propose that promotion of lipid droplet biogenesis can be seen as a potential protective mechanism against deleterious ceramides.<\/jats:p>","DOI":"10.3390\/ijms23179697","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T01:39:19Z","timestamp":1661737159000},"page":"9697","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Ceramide Acyl Chain Length and Its Relevance to Intracellular Lipid Regulation"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6281-7399","authenticated-orcid":false,"given":"Qing Wei Calvin","family":"Ho","sequence":"first","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore 308232, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2850-7308","authenticated-orcid":false,"given":"Xiaofeng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Center for Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Ali","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore 308232, Singapore"},{"name":"Singapore Eye Research Institute (SERI), Singapore General Hospital, Singapore 168751, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3892\/ijmm.2016.2600","article-title":"Intercellular and intracellular functions of ceramides and their metabolites in skin (Review)","volume":"38","author":"Cha","year":"2016","journal-title":"Int. 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