Macroautophagy (autophagy) maintains intracellular homeostasis by targeting damaged / dysregulated organelles for their transport to and degradation by the lysosome. Autophagy regulated gene 3 ( Atg3) enables autophagosome maturation which is required for the process of autophagy to occur. We reported that inducible depletion of Atg3 specifically in endothelial cells (ECs) impairs arterial function in the absence of metabolic disruptions (Cho et al., Cardiovasc Res, 2023). Sequestosome-1 (p62/SQSTM1) tethers proteins into the autophagic pathway for subsequent lysosomal degradation. The contribution from EC p62 to arterial and metabolic function is unknown and we addressed this. Adult male and female C57BL/6 mice with tamoxifen inducible depletion of p62 specifically in ECs ( p62EC−/−) were compared to littermate controls ( p62EC+/+). p62/18S mRNA expression was lower (p<0.05) in ECs but not vascular smooth muscle cells (VSM) from p62EC−/− [n=6] vs. p62EC+/+ [n=9] mice, whereas Beclin-1/18S was similar in ECs and VSM from both groups. Neither body composition, glucose disposal nor insulin tolerance were impacted by EC specific p62 depletion. Vascular contractile responses to: (i) phenylephrine mediated α1-activation and (ii) potassium chloride evoked L-type Ca2+ channel opening; and relaxation responses to (iii) acetylcholine (endothelium-dependent) and (iv) sodium nitroprusside (endothelium-independent); were similar between groups in mesenteric resistance arteries (isometric myography) and middle cerebral arteries (isobaric myography). Further, intrinsic arterial stiffness was not different between p62EC−/− [n=6] and p62EC+/+ [n=9] mice i.e., neither the elastic modulus nor stress vs. strain curves generated using segments of thoracic aorta were altered. These findings indicate EC specific p62 depletion does not impact arterial function or the indexes of systemic metabolism we measured. Because p62 is upregulated during cellular stress, it is possible that a challenge (e.g., hypoxia, ischemia) might be required to unmask a protective role for intact EC p62 and studies are ongoing to test this. Supported by AHA23PRE1025910 (SM); Rural and Underserved Utah Training Experience T32 (CG), Pacific Islander Research Internship Program (LG), NIHR01HL149870-01A1 (SB) and NIHRO1HL141540 (JDS). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.