P62, also known as Sequestosome-1, is a ubiquitin-binding adapter protein involved in the delivery of ubiquitin-bound protein and organelles to the autophagosome for lysosomal degradation during autophagy.  Mutations in p62 have been linked to Paget’s disease and neurodegenerative disorders.  P62 is typically degraded during the autophagy process, but can accumulate and/or overexpressed in autophagy-deficient cells.  Presence of p62 cytosolic aggregate is used as a marker for autophagy deficiency.  Defective autophagy increase oxidative stress and may play a role in tumorigenesis.  P62 immunohistochemistry (IHC) diagnostic utility was established for identifying hepatocellular carcinoma (HCC).  P62 demonstrates superior sensitivity for HCC compared against glypican-3.  Positive p62 staining was found in 100% of HCC but were negative in all non-tumor areas and cirrhotic nodules.  Furthermore, a panel consisting of p62, aminoacylase 1, and glypican-3 provides high sensitivity (93.8%) and specificity (95.2%) in the differential diagnosis between well differentiated HCC and high grade dysplastic nodules.    P62 expression can also aid in diagnosing drug-induced autophagic vacuolar myopathies.  An optimal threshold of at least 11.5% positive fibers provided 100% sensitivity and 100% specificity for autophagic myopathy.  While current diagnostic criteria require identification of autophagic vacuoles by electron microscopy, diagnosis with p62 IHC could expedite the process and reduce costliness and large sampling variance associated with electron microscopy.