Amyotrophic Lateral Sclerosis (ALS) is an almost selective motoneuron (MN) neurodegenerative disease in which the factors determining preferential involvement of MN are yet to be fully understood. TDP-43 nuclear clearance and aggregates are identified as a major component of the ubiquitinated neuronal cytoplasmic inclusions deposited in spinal motor neurons both in familiar and sALS patients. Since TDP43 protein contains the HSC70 recognition motif, and, therefore, chaperon mediated autophagy (CMA) function may represent a cellular mechanism to regulate TDP43 cytoplasmic turnover in cells. We have analyzed the expression of Lamp2a in MN, to explore if CMA may participate in ALS TDP43 proteinopathy. When 10 sections of cervical, thoracic, lumbar and sacral segments of the 6 control spinal cords, were processed by immunohistochemistry we have detected strong expression of Lamp2a in spinal MN of the anterior horn. We analyzed by immunohistochemistry the expression of Lam2a in the same regions of sALS patients’ spinal cords. Lamp2a immunopositivity was very weak in anterior horn MN. Interestingly, in the sacral levels, the MN of Onuf’s nucleus showed strong expression of Lamp2a, like the spinal and Onuf´s MN in control spinal cord. Macroautophagic marker LC3 immunohistochemistry did not show differences between control and sALS spinal cords. These results supports the requirement of high activity of CMA to maintain MN alive in ALS and reinforces the possibility that CMA may play a role in the selective pathophysiology of sALS in MN.Research supported by Cátedra para la esclerosis lateral amiotrófica "Gregoria Ramos Gil". 2023/CON/00024