Mapping protein aggregation pathways in vivo. An empirical energy landscape describing aggregation of the human ALS-causing protein, TDP-43, in living cells. The landscape illustrates how finite oligomers compete with liquid-liquid phase separation, and the two types of assemblies go on to nucleate two very distinct forms of amyloid. On the X and Y axes are structural coordinates that distinguish different self-assembled states. On the Z axis is the relative free energy of each state.