Studies in animal models of disease, human postmortem brain, cerebrospinal fluid, and iPSC-derived neurons (iSNs) suggest that GDE2 dysfunction and abnormal activation of Wnt signaling contribute to TDP-43 mislocalization and impaired nuclear function in ALS and ALS/FTD28,29. Here, GDPD5 is linked to amyotrophic lateral sclerosis.