This thesis investigates the role of Pannexin1 (Panx1) channels in lymphatic endothelial cells (LECs) and their impact on lymphatic function and atherosclerosis, with a focus on sex-dependent effects. Panx1 channels, which facilitate ion and molecule passage across cell membranes, show higher expression in male LECs. The study found that Panx1 deletion in male mice reduced lymphatic drainage, leading to fluid accumulation, while affecting lipid absorption in both sexes. In females, Panx1 deletion increased dendritic cell migration to lymph nodes. Additionally, Panx1 influenced atherosclerosis progression differently between sexes; male mice showed higher lipid levels, while females had more advanced atherosclerotic plaques. The findings suggest Panx1 channels play a crucial, sex-specific role in lymphatic function and atherosclerosis, highlighting their potential as therapeutic targets for personalized atherosclerosis treatment.