Several features of TDP-43 loss-of-function, such as splice alterations of STATHMIN2 (Melamed et al., 2019; Prudencio et al., 2020), UNC13A (Brown et al., 2022; Ma et al., 2022) and cryptic proteins have been isolated from the ALS patient’s cerebral spinal fluid (Irwin et al., 2023; Seddighi et al., 2023) underscoring the clinical relevance of loss of TDP-43 consequences for ALS. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.