Using cell-based models, including human induced pluripotent stem cell (hiPSC)-derived neurons, CRISPR-Cas9 technology, and transgenic PD/LBD mice, plus vetting in human postmortem brains, we found that S-nitrosylation of the autophagic receptor protein SQSTM1/p62 (forming SNO-SQSTM1/p62) inhibits autophagic flux, thus contributing to accumulation of misfolded SNCA/α-synuclein. The gene discussed is SQSTM1; the disease is Parkinson disease.