We present results for the one loop anomalous dimension matrix of flavor non-singlet twist-4 operators of lowest spin that contribute to the leading moment of the F 2 structure function in deep inelastic electron-nucleon scattering. We analyze the flavor structure of the anomalous dimension matrix and decompose the leading moment of F 2 into separate flavor channels. In addition to building on previous work with higher-twist operators, these results can provide a benchmark for future work that generalizes to include the higher moments as well. We include non-perturbative input from the lattice and phenomenological estimates of the twist-4 matrix elements and estimate the twist-4 contributions to the leading moment of F 2 . The results suggest that the overall twist-4 contribution may be suppressed due to either cancellations among the twist-4 terms or inherently small twist-4 matrix elements.