Considering the pathogenic role of aberrant TDP-43 homeostasis and cell cycle control failure in FTLD-TDP brain, it is suggested that CK-1δ could be potentially a novel therapeutic target for the treatment of FTLD-TDP and other TDP-43 proteinopathies, with special mention to ALS, considering that a clinical, genetic and neuropathological overlap exists between FTLD-TDP and ALS. This evidence concerns the gene TARDBP and proteostasis deficiencies.