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The role of CD36 in the regulation of lipid metabolism and ectopic fat accumulation emerges as a key area of interest. This review presents CD36 not only as a crucial facilitator of fatty acid uptake but also as a regulator of how and where excess lipids are stored. Ectopic fat accumulation\u2014lipid deposition in non\u2010adipose tissues such as the liver, muscle, and pancreas\u2014is linked to obesity\u2010related complications, including metabolic dysfunction\u2010associated steatotic liver disease (MASLD) and cardiovascular risk. Through CD36, tissues that normally play minor roles in lipid storage become overloaded, leading to metabolic dysfunction. We offer a fresh perspective on the adipose tissue expandability hypothesis, positioning CD36 as a regulator of adipose tissue's capacity to store lipids. Possibly, once adipose tissue reaches its expansion limit, CD36\u2010mediated mechanisms drive the spillover of lipids into ectopic sites, exacerbating obesity complications. This insight offers a transformative view of CD36 as a player in the metabolic tipping point between healthy fat storage and pathogenic fat deposition. The connection between CD36 and extracellular vesicles (EVs) hints at a broader network of inter\u2010tissue communication that could further amplify ectopic fat accumulation. Finally, we list evidence showing how CD36 genetics are related to the predisposition to develop and manage obesity. By understanding the role of CD36 in fat storage regulation, new personalized therapeutic strategies may emerge, targeting its pathways to prevent or reverse the metabolic damage caused by ectopic fat.<\/jats:p>","DOI":"10.1111\/obr.70039","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:14:56Z","timestamp":1764893696000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["CD36 and Its Role in Obesity"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6903-9972","authenticated-orcid":false,"given":"Nahuel","family":"Garcia","sequence":"first","affiliation":[{"name":"GECORP  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiken","family":"Mellergaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry Aalborg University Hospital  Aalborg Denmark"},{"name":"Department of 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