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We update the capabilities of the open-knowledge software instrument Modules for Experiments in Stellar Astrophysics (MESA). The newauto_diffmodule implements automatic differentiation inMESA, an enabling capability that alleviates the need for hard-coded analytic expressions or finite-difference approximations. We significantly enhance the treatment of the growth and decay of convection inMESAwith a new model for time-dependent convection, which is particularly important during late-stage nuclear burning in massive stars and electron-degenerate ignition events. We strengthenMESA’s implementation of the equation of state, and we quantify continued improvements to energy accounting and solver accuracy through a discussion of different energy equation features and enhancements. To improve the modeling of stars inMESA, we describe key updates to the treatment of stellar atmospheres, molecular opacities, Compton opacities, conductive opacities, element diffusion coefficients, and nuclear reaction rates. We introduce treatments of starspots, an important consideration for low-mass stars, and modifications for superadiabatic convection in radiation-dominated regions. We describe new approaches for increasing the efficiency of calculating monochromatic opacities and radiative levitation, and for increasing the efficiency of evolving the late stages of massive stars with a new operator-split nuclear burning mode. We close by discussing major updates toMESA’s software infrastructure that enhance source code development and community engagement.