In Neurofibromatosis type I (<i>NF1</i>)-deficient malignant peripheral nerve sheath tumor (MPNST) cells, <i>HSF1</i> loss induces widespread protein polyubiquitination, aggregation, and tumor-suppressive amyloidogenesis, yet is dispensable in non-transformed Schwann cells. Here, NF1 is linked to neurofibromatosis type 1.