TDP-43-dependent cryptic peptides, including the cryptic form of HDGFL2 among others, have emerged as potential biomarkers for ALS and FTD, reflecting loss of TDP-43 function consequent to its aggregation and phosphorylation in the cytoplasm along with TDP-43 nuclear depletion.63,64 Preliminary studies in both CSF and plasma have largely relied on cross-sectional samples collected from patients with clinically manifest ALS and individuals at elevated genetic risk for ALS. The gene discussed is HDGFL2; the disease is amyotrophic lateral sclerosis.