Given the evidence showing leptin levels related with overall survival and prognosis of ALS patients (Nagel et al., 2017), this study aimed to determine the impact of leptin treatment in the well validated TAR DNA binding protein (TDP‐43) A315T murine model of ALS TDP‐43 proteinopathy (Hatzipetros et al., 2014; Wegorzewska et al., 2009), which recapitulates several aspects of the human ALS, providing, to our knowledge, the first insights into the potential benefit of leptin to ALS. This evidence concerns the gene LEP and proteostasis deficiencies.