PROJECT SUMMARY (ABSTRACT) Water-washed diseases (infections related to inadequate water access and poor sanitation) are a preventable public health issue that continues to affect the 1.4 million people in the U.S. who still lack access to basic water and sanitation. The COVID-19 pandemic brought to the forefront a reminder that Native American households are 19 times more likely to lack indoor plumbing than White households. Historically, AN communities with a lower proportion of in-home piped water and sanitation services have disproportionately higher rates of respiratory and skin infections compared to plumbed communities, and these infection rates decreased after the installation of in-home water services in some communities. Inadequate funding, engineering challenges, affordability, and now climate change have hindered the installation and maintenance of centralized piped water and sewer systems in remote Alaska. There is therefore an urgent need to evaluate whether novel, targeted water, sanitation, and hygiene (WASH) interventions reduce water-wash disease disparities. To address this need, this study will evaluate the impact of a targeted WASH intervention developed specifically for American Indian/Alaska Native (AI/AN) communities, known as the Portable Alternative Sanitation System (PASS), on water use, waste management, water-wash disease and well-being (defined by both biomedical and locally- defined categories) over time in AN households. We will do this through two Specific Aims: 1) Characterize the lived experiences of household water- and sanitation security (HWSS), health, and well-being in remote AN households across the water and sanitation service spectrum using community-based measures and 2) Evaluate the impact of the PASS on in-home water storage and use, quality of life, water security and reliability, and prevalence of water-washed diseases. Through this mixed methods, longitudinal study, we will provide evidence that demonstrates how a targeted WASH intervention affects water-wash diseases, in-home water use and waste management, and overall well-being in AIAN communities. This will also enable tribes, tribal health organizations, and related stakeholders beyond Alaska to evaluate the PASS system to decide if it is appropriate for their own communities. This study builds on our previous work in the community of Kivalina with a greater sample size, comparison of data from piped and unpiped households, and longitudinal data from the post-COVID era. To our knowledge, this is the first longitudinal evaluation of how an in-home point-of-use water treatment and waterless toilet system affects household water and sanitation security, health, and well-being in an Arctic, Indigenous context.