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Increasing evidence suggests that circadian regulation intersects with multiple cellular processes implicated in AD pathogenesis, including autophagy and ferroptosis. Among these mechanisms, clockophagy, an SQSTM1\/p62-mediated selective autophagic process involved in BMAL1 degradation, has recently emerged as a potential molecular link between circadian regulation and cellular stress responses. In this review, we summarize current evidence connecting sleep disruption, circadian dysfunction, lipid peroxidation, and ferroptotic susceptibility in AD, while highlighting the current limitations of mechanistic evidence. We further discuss the molecular basis of clockophagy and its potential relationship with BMAL1 regulation, oxidative lipid damage, and ferroptosis. Collectively, clockophagy is currently viewed as an emerging hypothesis that may contribute to AD-related pathological processes. Finally, we discuss potential therapeutic implications, including approaches targeting sleep and circadian organization, BMAL1-associated regulatory pathways, and lipid oxidative stress. Further studies are required to determine whether modulation of clockophagy can influence AD-related neurodegenerative processes.<\/jats:p>","DOI":"10.3390\/cells15191721","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:17:54Z","timestamp":1790065074000},"page":"1721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clockophagy in Alzheimer\u2019s Disease: An Emerging Hypothesis Linking Circadian Dysfunction to Ferroptotic Vulnerability"],"prefix":"10.3390","volume":"15","author":[{"given":"Jianqin","family":"Mao","sequence":"first","affiliation":[{"name":"The First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yudan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Health Science Center, Hubei Minzu University, Enshi 445000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Engineering Research Center, Hubei University of Chinese Medicine, Wuhan 430065, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2005-8408","authenticated-orcid":false,"given":"Dongdong","family":"Qin","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S1474-4422(25)00116-4","article-title":"Protective genetic variants against Alzheimer\u2019s disease","volume":"24","author":"Marino","year":"2025","journal-title":"Lancet Neurol."},{"key":"ref_2","unstructured":"GBD 2019 Dementia Forecasting Collaborators (2022). 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