This study shows that TAF15, an RNA-binding protein and the main fibrillar component in a subset of frontotemporal lobar degeneration (FTLD) cases, forms amyloid fibrils under physiological conditions and propagates in a prion-like manner, with defined aggregation-prone motifs driving fibril stability and seeding; recombinant and patient-derived aggregates seeded cellular biosensors, while FUS did not cross-seed TAF15. Flow Induced Dispersion Analysis (FIDA) was used to measure the thermodynamic stability of TAF15 fibrils, quantifying the soluble fraction released during urea-induced disassembly to derive the free energy of depolymerization. It is an example of using FIDA to quantify a protein in solution to derive fibril thermodynamic stability.