The role of the Karakorum fault zone (KFZ) is debated. South of 33°N, ongoing dextral-oblique slip along the SW edge of the Gar basin exhumes metamorphic and magmatic rocks of the Ayilari range. Minerals have recorded a continuum of deformation from temperatures >600–400°C down to <250_C. The 40Ar/39Ar ages, the oldest being 21.2 ± 1.0 Ma, yield minimum estimates for the initiation of the KFZ. These are in agreement with the U-Th/Pb ages constraining the onset of deformation at ca 25–22 Ma. Thermochronologic results show slow cooling for the period ca 21– 14 Ma, followed by rapid cooling between 14 and 4 Ma. These data demonstrate that right-lateral motion was in progress in the early Miocene and that shear continued at least until 4 Ma, pointing to >20 Ma of deformation along the fault. Greenschist facies deformation superimposed upon the medium- to high-grade deformation marks a kinematic change from pure dextral to dextral-normal motion associated with the onset of rapid cooling. At the regional scale, the coexistence of transtension in the Gar basin with transpression documented along the Pangong range farther north suggests another example of the ‘‘zipper tectonics'' model developed along the Red River fault. The kinematic shift induced the rise of the Ayilari range starting at 16–12 Ma and the incision of major river courses. The Indus River might have become captive of the relief at this time. The river's 120 km of apparent offset implies dextral motion at a long-term rate of ca 8.5 ± 1.5 mm/yr.