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The role of the Karakoram fault (KKF) in evolution of the Tibetan–Himalayan orogenic belt is controversial. Some consider the KKF to be a stable, long-lived feature with several hundred kilometres of offset along its entire current trace, whereas others interpret it as having propagated along its NW–SE trend since initiation at ∼16 Ma with small-scale slip being gradually absorbed by transfer structures along the fault trace. Here we report new zircon U–Pb and mica40Ar/39Ar ages related to the Ayi Shan detachment to better constrain the activity of the KKF in southwestern Tibet. The zircon U–Pb data show migmatite ages of 489, 478, and 435 Ma from the footwall of the Ayi Shan detachment involved in the KKF ductile shear zone. Mylonitized migmatite in the South Ayilari did not record any KKF activity. Similarly aged magmatic and metamorphic information recorded in mylonites and undeformed rocks of the Animaqing Group around the North Ayilari also rules out the effect of KKF movement on zircon growth. Cenozoic information recorded in North Ayilari zircons evidently resulted from Trans-Himalayan magmatic belt (THB) magmatism during 45–50 Ma and 32–25 Ma. Four mica dates from the same mylonitized samples all cluster around 12 Ma. Combined zircon U–Pb and mica40Ar/39Ar ages from the mylonites and undeformed rocks support the hypothesis that the KKF imposed a structural fabric on the rocks of the Animaqing Group and the THB granites at around 12 Ma in the Ayilari Range. Chronologic, kinematic, and geometric studies demonstrate that the fault propagated southeastward into SW Tibet at 12 Ma. [ABSTRACT FROM PUBLISHER]