Electron and muon deep inelastic scattering (DIS) experiments off nuclear targets demonstrated significant nuclear effects on parton distribution functions at energies and momenta much higher than those involved in typical nuclear ground-state processes, ruling out the naive picture of the nucleus as a system of quasifree nucleons. A quantitative explanation of the observed effects requires the presence of an in-medium nuclear modification of parton distribution functions, extending beyond the traditional Fermi motion and binding correction. We will present a number of applications including lepton-nucleus DIS, Drell-Yan production in proton-nucleus collisions,  and $W^\pm, Z^0$ boson production in p+Pb collisions at the LHC. We will also discuss nuclear corrections in the deuteron and their impact on the determination of $d/u$ ratio from global QCD fits.