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Over the past 5 years, mounting evidence has revealed its ubiquity across biological kingdoms, from tidal marine organisms and cyanobacteria to plants, microbiomes, and mammals, including humans, manifesting as intrinsic oscillations in gene expression, metabolism, and behavior that often persist independently of circadian control. In mammals, this rhythm is driven by a cell\u2010autonomous oscillator centered on the XBP1s (X\u2010box binding protein 1)\/IRE1\u03b1 (Inositol requiring enzyme 1 alpha) axis, orchestrating endoplasmic reticulum stress responses and lipid homeostasis through negative feedback regulation, further reinforced by metabolic coupling and bidirectional crosstalk with circadian pathways. Functionally, 12\u2010h oscillations act as a secondary temporal layer that ensures bimodal photostatic and energetic homeostasis, synchronizing multi\u2010organ physiology across the day\u2013night transition. Pathologically, disruption of this rhythm contributes to metabolic syndromes (e.g., NAFLD (non\u2010alcoholic fatty liver disease), diabetes), neuropsychiatric disorders (e.g., schizophrenia), and age\u2010related dysfunctions, particularly within ocular and immune systems. Despite accumulating correlative and model\u2010based evidence, causal mechanisms remain insufficiently defined, and human data are limited. Future work integrating multi\u2010omics chrono profiling, comparative genomics, and clinical chronotherapeutic trials will be critical to delineate this semidiurnal oscillator's molecular architecture and translational potential, thereby advancing precision chrono medicine and expanding the current paradigm of biological timing.<\/jats:p>","DOI":"10.1002\/cbf.70195","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:14:09Z","timestamp":1773810849000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Unveiling the 12\u2010Hour Ultradian Rhythm: Biological Foundations, Mechanistic Insights, and Potential Applications"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2206-4338","authenticated-orcid":false,"given":"Jiayi","family":"Song","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Affiliated Hospital of Shandong Second 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