For example, nuclear depletion of TDP-43, a hallmark of ALS, results in alternative splicing of HNRNPA1 itself and production of A1-B, the A1 isoform with an expanded PrLD of increased aggregative propensity, creating a positive feedback loop of aggregation and nuclear depletion of PrLD-containing proteins [54]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.