Neurodegenerative tauopathies are characterized by pathological tau aggregation, often associated with cellular protein degradation defects.. The autophagy-lysosome system is essential for degrading aggregated proteins, and its failure can directly contribute to tau aggregation and neurodegeneration. Central to this process is the protein p62, which shuttles ubiquitinated proteins and organelles, including pathological tau, to autophagosomes for lysosomal degradation. Mutations in p62 disrupt this crucial function, leading to proteostasis breakdown. Fibroblasts obtained from patient dermal punches provide a powerful disease model as they retain the patient's specific epigenetic landscape. To investigate whether autophagy defects can be identified in patients derived fibroblasts as a strategy for disease detection, we used fibroblasts obtained from a primary tauopathy patient carrying the heterozygous mutation PRO392LEU in the ubiquitin-associated (UBA) domain of p62 (p62-P392L) and control donors.Preliminary analysis revealed increased cell area in p62-P392L patient; decreased Tau5 without PHF1 increase. p62-P392L fibroblasts showed reduced p62 by immuno/WB. LC3 levels and LC3II/I ratio by WB were increased. NH4Cl exposure highlighted these changes. Lysotracker showed more vesicles per cell.These findings show p62-P392L fibroblasts recapitulate impaired autophagy, offering a model to study proteostasis disruption in tauopathies