Lysosomal Cathepsin A (CathA) is a multifunctional enzyme with independent catalytic and protective functions. It has a serine carboxypeptidase activity in acidic pH conditions for the degradation of short bioactive peptides that are vasoactive peptides including endothelin-1, angiotensin-I, bradykinin and neuropeptides including oxytocin and substance P. Lysosomal CathA enzyme also forms a lysosomal multienzyme complex (LMC) with α-neuraminidase (Neu1) and ß-Galactosidase (ß-Gal) enzymes to protect them from hydrolytic degradation in lysosomes and due to its protective function. Genetic defects in the lysosomal CathA enzyme causes a rare lysosomal storage disorder, Galactosialidosis (OMIM #256540), with secondary deficiencies of Neu1 and ß-Gal enzymes. Catalytically inactive Cathepsin A knock-in mouse model, CathAS190A has point mutation in the active catalytic site which serine was replace with alanine amino acid. Accumulation of short bioactive peptides has been reported in previous studies in different tissues of the CathAS190A mouse model. In this thesis study, investigation the role of the lysosomal CathA enzyme in the regulation of autophagic flux in neuroglia and fibroblast cell lines derived from CathAS190A mice was aimed. For this aim; RT-PCR, Western Blot and Immunocytochemical analyses were for performed for autophagy markers. Thesis study results have exhibited that catalytically deficient CathA causes the impairment in autophagic machinery with secondary accumulation of autophagic substrates and alterations in the expression of the autophagy marker genes. Accumulation of the short bioactive peptides due to the catalytically inactive CathA enzyme may be related to to impaired autophagic flux. Autophagy-inducing Rapamycin and Starvation treatment conditions may restore the impaired autophagic flux due to catalytically inactive CathA enzyme with the clearance of accumulation of secondary autophagic substrates.