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Layer management
Painter computes the layer stack from the bottom to the top. So, if you make changes to the top layer on the stack, Painter only needs to compute the changes of that layer. However, if you make a change to a layer at the bottom of the stack, Painter needs to compute all of the layers above that layer to calculate the final result.
This is similar to changing a Substance 3D Designer node at the beginning of the graph - all subsequent nodes need to be recalculated.
In order to avoid slowdowns when making changes at a lower level in the layer stack, you can hide layers above the edited layer until you have finished making your adjustments. Painter doesn't calculate hidden layers, so it's as if you're editing the top layer in the stack. This way, the layers above will only be computed when you unhide them, rather than after every change you make.
You can also group all the layers above in one individual group with the blending mode set to Normal. Doing so will avoid computing the layers/group individually for the engine. While the Substance 3D Painter engine employs multiple algorithms to determine what needs to be computed or not, grouping layers manually can help improve performance.