Although the underlying mechanisms are still unclear, the preponderance of ALS/FTD-associated mutations in FUS interferes with its nuclear import and folding, leading to the accumulation of cytosolic FUS aggregates that disrupt cellular function through loss-of-function (LOF) and gain-of function mechanisms impacting protein translation and nuclear transport among other processes (2, 8, 9, 10, 11). The gene discussed is FUS; the disease is frontotemporal dementia.