SQSTM1 also known as p62, ZIP is a multifunctional adaptor protein involved in various cellular processes, including autophagy, where SQSTM1 facilitates the selective degradation of ubiquitinated proteins by interacting with LC3 on autophagosomes. SQSTM1 interacts with key signaling proteins such as TRAF6, which plays a pivotal role in the NF-κB signaling pathway, and Keap1, which regulates the Nrf2 pathway involved in oxidative stress responses. These interactions are crucial for maintaining cellular homeostasis and regulating inflammation, apoptosis, and oxidative stress responses. SQSTM1′s binding to ubiquitinated proteins is further modulated by post-translational modifications, including phosphorylation and ubiquitination, which enhance binding affinity and functional versatility in signaling pathways and autophagic flux.