p62 / SQSTM1

p62, encoded by the SQSTM1 gene, is a multifunctional scaffold and selective autophagy receptor that recognises ubiquitinated cargo through its UBA domain and delivers it to autophagosomes by simultaneously binding LC3/GABARAP proteins via its LC3-interacting region (LIR). Beyond cargo triage, p62 integrates cellular stress signals: it activates the Nrf2 antioxidant response by sequestering the Keap1 adaptor and promotes mTORC1 activity by recruiting TRAF6 to catalyse K63-ubiquitination of mTOR (facilitating lysosomal translocation) and by amino-acid-dependent scaffolding of Raptor. Because autophagic flux normally degrades p62, its cytoplasmic accumulation — observed in aged tissues, alcoholic liver disease, and many cancers — serves as a practical readout of impaired autophagy and is a histopathological hallmark of ubiquitin-positive inclusion bodies.