The imbalance of protein homeostasis (proteostasis) is thought to be a major driver of pathology in many neurodegenerative diseases that involve widespread protein aggregation. One hypothesis is that the aggregation-prone disease proteins redirect protein folding quality control resources away from normal housekeeping folding functions, which can lead to an accumulation of unfolded proteins that subsequently aggregate. However, it is still not known which proteins in the proteome are most vulnerable to unfolding and aggregation under proteostasis stress. In this ongoing project, we describe our results probing two cellular models of proteostasis stresses. In one we defined how formation of Huntingtin (Htt) inclusions leads to broader proteome aggregation in trans. In the other, we induced ER stress with tunicamycin, which causes a backlog of unfolded proteins in the ER and the ER stress response. We discovered with tunicamycin several key proteins involved in the stress response to be involved to become more insoluble. This poster will describe these findings and broader implications.