Protein aggregation disorders (PADs) are characterized by accumulation of misfolded proteins leading to cell dysfunction and tissue degeneration. A network of cellular processes impacts cellular proteostasis, including protein synthesis, folding, and breakdown. Pathogenic protein aggregates, the hallmark of a variety of adult-onset diseases, can be caused by genetic mutations that increase a protein’s aggregation propensity, in combination with proteostasis-associated cellular mechanisms. Protein aggregates can be found across all tissues and cell types, but pathogenic protein aggregates are most often found in post-mitotic cells of the neuromuscular system. Except for treatment strategies that aid in improving the quality of life, currently, no curative treatments are available for many protein aggregation disorders. Our as-yet insufficient understanding of the processes leading to protein aggregation impedes the development of innovative treatment strategies. A big challenge in such research is that a full understanding requires in-depth studies from the organismal, cellular, molecular, to atomic level. Thus, we need multidisciplinary research of protein aggregation in humans and in disease-relevant models, to open novel avenues for therapeutical development and to accelerate translational research. Here, we advocate for multidisciplinary networks that cross disease-specific borders and discuss the requirements for collaboration and communication across traditional research niches. Ultimately, this will advance our understanding, diagnosis, and treatment of these debilitating protein aggregation diseases.