Sequestosome1/p62/A170 (SQSTM1) is a multifunctional regulator of cell signaling and metabolism with an ability to modulate targeted degradation of proteins through autophagy. SQSTM1 implements its functions through physical interactions with different types of proteins including atypical PKCs, non-receptor type tyrosine kinase p56Lck (Lck), polyubiquitin and autophagosomal factor LC3. One of the notable physiological functions of SQSTM1 is the regulation of redox sensitive voltage-gated potassium (Kv) channels which modulate membrane potential, signal integration and neurotransmitter release. Kv channels are composed of α and β subunits, (Kvα)4 and (Kvβ)4. Previous studies have established that SQSTM1 scaffolds PKCζ, enhancing phosphorylation of Kvβ. Both PKCζ and SQSTM1 play key roles in acute hypoxia-induced Kv channel inactivation in pulmonary artery. SQSTM1 is an oxidative stress inducible protein regulated by transcription factor Nrf2, a master regulator of antioxidant system (1). The expression levels of SQSTM1 in vascular cells are up-regulated by atherogenic stimuli, such as oxidized low density lipoprotein and 4-hydroxynonenal, suggesting SQSTM1 has a protective role against oxidative stress (2). We have examined the role of SQSTM1 in neointimal hyperplasia and vascular remodeling in vivo following carotid artery ligation. Neointimal hyperplasia was markedly enhanced near the ligation sites after 3 weeks in SQSTM1-/- compared with wild-type (SQSTM1+/+) mice. The intimal area and stenotic ratio were, respectively, 2.1- and 1.7-fold higher in SQSTM1-/- mice, indicating enhanced proliferation of vascular smooth muscle cells (SMCs). We found that migration of aortic SQSTM1-/- SMCs was enhanced compared to wild type SMCs and that they proliferated more rapidly in response to fetal calf serum and attained 2-3-fold higher cell densities compared to wild type SMCs. The enhanced proliferation of SQSTM1-/- aortic SMCs in vitro highlights a novel role for SQSTM1 in suppressing smooth muscle migration and proliferation following vascular injury (3). Recent studies have revealed the role of Kv1.3 channels in enhancing migration and proliferation of arterial SMCs (4). As Kv1.3 channels provide a signaling platform and may thereby modulate the migration and proliferation of arterial SMCs and are recognized as a therapeutic target for treatment of restenosis. Based on these studies, we highlight the molecular mechanisms by which SQSTM1 suppresses proliferation of arterial smooth muscle cells and neointimal hyperplasia following carotid artery ligation.