SUGP1 and amyotrophic lateral sclerosis: In the early stages of ALS, human induced pluripotent stem cell-derived motor neurons (MNs) are found that NOVA1 expression was significantly upregulated but functionally deficient, indicating that the RBP splicing network is disrupted in a complex manner early in the onset of ALS.403 As ALS progresses, NOVA1 levels gradually decrease, and RBP TAR DNA binding protein 43 (TDP43) gradually accumulates and functionally enhances.404 The loss of TDP43 in the nucleus and cytoplasmic accumulation is a characteristic of late-stage ALS.