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Despite the presence of these typical subcellular inclusions under various conditions, relatively little is known about their origins, roles, and effects on liver cell and tissue health. Pathologists use the presence of lipofuscin, in combination with other markers, to achieve differential diagnosis across various diseases. Routine histological stains reveal characteristic irregular shaped intracellular inclusions of lipofuscin that cannot be missed. Moreover, lipofuscin is autofluorescent and in transmission electron microscopy it appears in the cytoplasm as irregularly shaped structures containing fat and floccular material with varying electron density. Herein, we discuss the current state of knowledge concerning the origin and function of this pigment in the liver. Lipofuscin can distinctively be found in liver, although it has also been reported in cells in the heart, brain, and eye. Its biochemical composition is heterogeneous and varies depending on the tissue and the age of the organism. The liver parenchymal cells have efficient cellular waste disposal mechanisms, but they are still susceptible to aging. Lipofuscin accumulation in the liver may result from ongoing oxidative damage and impaired hepatic detoxification leading to cellular stress.<\/jats:p>","DOI":"10.1007\/s00418-026-02502-9","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T09:35:04Z","timestamp":1782380104000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["From lipofuscin accumulation to cellular dysfunction: a focus on liver pathophysiology"],"prefix":"10.1007","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5222-0895","authenticated-orcid":false,"given":"Filip","family":"Braet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie","family":"Wisse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ger H.","family":"Koek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J.","family":"Shami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-3771","authenticated-orcid":false,"given":"Amy","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"issue":"7360","key":"2502_CR1","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/S0140-6736(64)90513-6","volume":"284","author":"C Abrahams","year":"1964","unstructured":"Abrahams C, Wheatley A, Rubenstein AH, Stables D (1964) Hepatocellular lipofuscin after excessive ingestion of analgesics. 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